{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:06:32Z","timestamp":1789445192908,"version":"build-2803163510"},"reference-count":214,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurotox Res"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1007\/s12640-020-00232-x","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T05:02:42Z","timestamp":1592456562000},"page":"833-849","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Exploring the Role of PSEN Mutations in the Pathogenesis of Alzheimer\u2019s Disease"],"prefix":"10.1007","volume":"38","author":[{"given":"Md. Tanvir","family":"Kabir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-7840","authenticated-orcid":false,"given":"Md. Sahab","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinnat Ruksana","family":"Setu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghulam Md","family":"Ashraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May N.","family":"Bin-Jumah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed M.","family":"Abdel-Daim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"232_CR1","doi-asserted-by":"publisher","unstructured":"Al Mamun A, Uddin MS (2020) KDS2010: a potent highly selective and reversible MAO-B inhibitor to abate Alzheimer\u2019s disease. Comb Chem High Throughput Screen 23. https:\/\/doi.org\/10.2174\/1386207323666200117103144","DOI":"10.2174\/1386207323666200117103144"},{"key":"232_CR2","doi-asserted-by":"publisher","first-page":"5086250","DOI":"10.1155\/2020\/5086250","volume":"2020a","author":"A Al Mamun","year":"2020","unstructured":"Al Mamun A, Sahab Uddin M, Fahim Bin Bashar M et al (2020a) Molecular insight into the therapeutic promise of targeting APOE4 for Alzheimer\u2019s disease. Oxidative Med Cell Longev 2020a:5086250. https:\/\/doi.org\/10.1155\/2020\/5086250","journal-title":"Oxidative Med Cell Longev"},{"key":"232_CR3","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.4103\/1673-5374.274329","volume":"15","author":"A Al Mamun","year":"2020","unstructured":"Al Mamun A, Uddin MS, Mathew B, Ashraf GM (2020b) Toxic Tau: structural origins of Tau aggregation in Alzheimer\u2019s disease. Neural Regen Res 15:1417\u20131420. https:\/\/doi.org\/10.4103\/1673-5374.274329","journal-title":"Neural Regen Res"},{"key":"232_CR4","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s12640-020-00185-1","volume":"38","author":"A Al Mamun","year":"2020","unstructured":"Al Mamun A, Uddin MS, Kabir MT et al (2020c) Exploring the promise of targeting ubiquitin-proteasome system to combat Alzheimer\u2019s disease. Neurotox Res 38:8\u201317. https:\/\/doi.org\/10.1007\/s12640-020-00185-1","journal-title":"Neurotox Res"},{"key":"232_CR5","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/S0304-3940(97)00950-6","volume":"240","author":"J Aldudo","year":"1998","unstructured":"Aldudo J, Bullido MJ, Arbizu T et al (1998) Identification of a novel mutation (Leu282Arg) of the human presenilin 1 gene in Alzheimer\u2019s disease. Neurosci Lett 240:174\u2013176. https:\/\/doi.org\/10.1016\/S0304-3940(97)00950-6","journal-title":"Neurosci Lett"},{"key":"232_CR6","unstructured":"ALZFORUM (2020) Mutation: PSEN-1. https:\/\/www.alzforum.org\/mutations\/psen-1. Accessed 29 Apr 2020"},{"key":"232_CR7","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.jalz.2011.02.004","volume":"7","author":"Alzheimer\u2019s Association","year":"2011","unstructured":"Alzheimer\u2019s Association (2011) 2011 Alzheimer\u2019s disease facts and figures. Alzheimers Dement 7:208\u2013244. https:\/\/doi.org\/10.1016\/j.jalz.2011.02.004","journal-title":"Alzheimers Dement"},{"key":"232_CR8","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1001\/archneur.55.5.698","volume":"55","author":"K Axelman","year":"1998","unstructured":"Axelman K, Basun H, Lannfelt L (1998) Wide range of disease onset in a family with Alzheimer disease and a His163Tyr mutation in the Presenilin-1 gene. Arch Neurol 55:698. https:\/\/doi.org\/10.1001\/archneur.55.5.698","journal-title":"Arch Neurol"},{"key":"232_CR9","first-page":"357","volume":"40","author":"Y Bai","year":"2011","unstructured":"Bai Y, Tian J, Quan W, Maeda K (2011) Association of mutations of Presenilin-2 gene and sporadic Alzheimer\u2019s disease. J China Med Univ 40:357\u2013363","journal-title":"J China Med Univ"},{"key":"232_CR10","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/nature14892","volume":"525","author":"X Bai","year":"2015","unstructured":"Bai X, Yan C, Yang G et al (2015) An atomic structure of human \u03b3-secretase. Nature 525:212\u2013217. https:\/\/doi.org\/10.1038\/nature14892","journal-title":"Nature"},{"key":"232_CR11","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/s12015-018-9811-3","volume":"14","author":"R Ben Jehuda","year":"2018","unstructured":"Ben Jehuda R, Shemer Y, Binah O (2018) Genome editing in induced pluripotent stem cells using CRISPR\/Cas9. Stem Cell Rev Rep 14:323\u2013336","journal-title":"Stem Cell Rev Rep"},{"key":"232_CR12","doi-asserted-by":"publisher","first-page":"45564","DOI":"10.1074\/jbc.M407717200","volume":"279","author":"A Bergman","year":"2004","unstructured":"Bergman A, Laudon H, Winblad B et al (2004) The extreme C terminus of Presenilin 1 is essential for \u03b3-secretase complex assembly and activity. J Biol Chem 279:45564\u201345572. https:\/\/doi.org\/10.1074\/jbc.M407717200","journal-title":"J Biol Chem"},{"key":"232_CR13","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1007\/s00415-008-0764-3","volume":"255","author":"L Bernardi","year":"2008","unstructured":"Bernardi L, Tomaino C, Anfossi M et al (2008) Late onset familial Alzheimer\u2019s disease: novel presenilin 2 mutation and PS1 E318G polymorphism. J Neurol 255:604\u2013606","journal-title":"J Neurol"},{"issue":"6","key":"232_CR14","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1002\/(SICI)1098-1004(1998)11:6<481::AID-HUMU12>3.0.CO;2-Q","volume":"11","author":"R Besan\u00e7on","year":"1998","unstructured":"Besan\u00e7on R, Lorenzi A, Cruts M et al (1998) Missense mutation in exon 11 (Codon 378) of the presenilin-1 gene in a French family with early-onset Alzheimer\u2019s disease and transmission study by mismatch enhanced allele specific amplification mutations in brief no. 141. Hum Mutat 11(6):481. https:\/\/doi.org\/10.1002\/(SICI)1098-1004(1998)11:6<481::AID-HUMU12>3.0.CO;2-Q","journal-title":"Hum Mutat"},{"key":"232_CR15","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1002\/ana.10760","volume":"54","author":"G Binetti","year":"2003","unstructured":"Binetti G, Signorini S, Squitti R et al (2003) Atypical dementia associated with a novel Presenilin-2 mutation. Ann Neurol 54:832\u2013836. https:\/\/doi.org\/10.1002\/ana.10760","journal-title":"Ann Neurol"},{"key":"232_CR16","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/S0896-6273(00)80230-5","volume":"17","author":"DR Borchelt","year":"1996","unstructured":"Borchelt DR, Thinakaran G, Eckman CB et al (1996) Familial Alzheimer\u2019s disease-linked presenilin I variants elevate a\u03b21- 42\/1-40 ratio in vitro and in vivo. Neuron 17:1005\u20131013. https:\/\/doi.org\/10.1016\/S0896-6273(00)80230-5","journal-title":"Neuron"},{"key":"232_CR17","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1080\/07853890802186905","volume":"40","author":"N Brouwers","year":"2008","unstructured":"Brouwers N, Sleegers K, Van Broeckhoven C (2008) Molecular genetics of Alzheimer\u2019s disease: an update. Ann Med 40:562\u2013583","journal-title":"Ann Med"},{"key":"232_CR18","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.2147\/CIA.S85808","volume":"10","author":"Y Cai","year":"2015","unstructured":"Cai Y, An SSA, Kim S (2015) Mutations in presenilin 2 and its implications in Alzheimer\u2019s disease and other dementia-associated disorders. Clin Interv Aging 10:1163\u20131172. https:\/\/doi.org\/10.2147\/CIA.S85808","journal-title":"Clin Interv Aging"},{"key":"232_CR19","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.1093\/hmg\/4.12.2373","volume":"4","author":"D Campion","year":"1995","unstructured":"Campion D, Flaman J-M, Brice A et al (1995) Mutations of the presenilin I gene in families with early-onset Alzheimer\u2019s disease. Hum Mol Genet 4:2373\u20132377. https:\/\/doi.org\/10.1093\/hmg\/4.12.2373","journal-title":"Hum Mol Genet"},{"key":"232_CR20","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1097\/00001756-199607080-00009","volume":"7","author":"D Campion","year":"1996","unstructured":"Campion D, Brice A, Dumanchin C et al (1996) A novel presenilin 1 mutation resulting in familial Alzheimer\u2019s disease with an onset age of 29 years. Neuroreport 7:1582\u20131584. https:\/\/doi.org\/10.1097\/00001756-199607080-00009","journal-title":"Neuroreport"},{"key":"232_CR21","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1086\/302553","volume":"65","author":"D Campion","year":"1999","unstructured":"Campion D, Dumanchin C, Hannequin D et al (1999) Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet 65:664\u2013670. https:\/\/doi.org\/10.1086\/302553","journal-title":"Am J Hum Genet"},{"key":"232_CR22","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.disamonth.2010.06.001","volume":"56","author":"RJ Castellani","year":"2010","unstructured":"Castellani RJ, Rolston RK, Smith MA (2010) Alzheimer disease. Disease-a-Month 56:484\u2013546","journal-title":"Disease-a-Month"},{"key":"232_CR23","doi-asserted-by":"publisher","first-page":"9458","DOI":"10.1523\/JNEUROSCI.2047-09.2009","volume":"29","author":"S Chakroborty","year":"2009","unstructured":"Chakroborty S, Goussakov I, Miller MB, Stutzmann GE (2009) Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice. J Neurosci 29:9458\u20139470. https:\/\/doi.org\/10.1523\/JNEUROSCI.2047-09.2009","journal-title":"J Neurosci"},{"key":"232_CR24","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/35087069","volume":"3","author":"F Chen","year":"2001","unstructured":"Chen F, Yu G, Arawaka S et al (2001) Nicastrin binds to membrane-tethered Notch. Nat Cell Biol 3:751\u2013754. https:\/\/doi.org\/10.1038\/35087069","journal-title":"Nat Cell Biol"},{"key":"232_CR25","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1038\/nature04667","volume":"440","author":"F Chen","year":"2006","unstructured":"Chen F, Hasegawa H, Schmitt-Ulms G et al (2006) TMP21 is a presenilin complex component that modulates \u03b3-secretase but not \u025b-secretase activity. Nature 440:1208\u20131212. https:\/\/doi.org\/10.1038\/nature04667","journal-title":"Nature"},{"key":"232_CR26","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/nm0197-67","volume":"3","author":"M Citron","year":"1997","unstructured":"Citron M, Westaway D, Xia W et al (1997) Mutant presenilins of Alzheimer\u2019s disease increase production of 42-residue amyloid \u03b2-protein in both transfected cells and transgenic mice. Nat Med 3:67\u201372. https:\/\/doi.org\/10.1038\/nm0197-67","journal-title":"Nat Med"},{"key":"232_CR27","doi-asserted-by":"publisher","first-page":"T583","DOI":"10.1016\/j.jalz.2008.05.1780","volume":"4","author":"J Clarim\u00f3n","year":"2008","unstructured":"Clarim\u00f3n J, Guerreiro R, Lle\u00f3 A et al (2008) P3-213: genetic screening in a large cohort of early-onset Alzheimer\u2019s disease patients from Spain: novel mutations in the amyloid precursor protein and presenilines. Alzheimers Dement 4:T583. https:\/\/doi.org\/10.1016\/j.jalz.2008.05.1780","journal-title":"Alzheimers Dement"},{"key":"232_CR28","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/ng1095-219","volume":"11","author":"RF Clark","year":"1995","unstructured":"Clark RF, Hutton M, Fuldner M et al (1995) The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet 11:219\u2013222. https:\/\/doi.org\/10.1038\/ng1095-219","journal-title":"Nat Genet"},{"key":"232_CR29","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1136\/jnnp.2003.020198","volume":"75","author":"EA Croes","year":"2004","unstructured":"Croes EA, Theuns J, Houwing-Duistermaat JJ et al (2004) Octapeptide repeat insertions in the prion protein gene and early onset dementia. J Neurol Neurosurg Psychiatry 75:1166\u20131170. https:\/\/doi.org\/10.1136\/jnnp.2003.020198","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"232_CR30","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/ana.410420121","volume":"42","author":"R Crook","year":"1997","unstructured":"Crook R, Ellis R, Shanks M et al (1997) Early-onset Alzheimer\u2019s disease with a presenilin-1 mutation at the site corresponding to the volga German presenilin-2 mutation. Ann Neurol 42:124\u2013128. https:\/\/doi.org\/10.1002\/ana.410420121","journal-title":"Ann Neurol"},{"key":"232_CR31","doi-asserted-by":"publisher","first-page":"e31039","DOI":"10.1371\/journal.pone.0031039","volume":"7","author":"C Cruchaga","year":"2012","unstructured":"Cruchaga C, Chakraverty S, Mayo K et al (2012) Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer\u2019s disease families. PLoS One 7:e31039. https:\/\/doi.org\/10.1371\/journal.pone.0031039","journal-title":"PLoS One"},{"key":"232_CR32","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1093\/hmg\/4.12.2363","volume":"4","author":"M Cruts","year":"1995","unstructured":"Cruts M, Backhovens H, Wang SY et al (1995) Molecular genetic analysis of familial early-onset Alzheimer\u2019s disease linked to chromosome 14q24.3. Hum Mol Genet 4:2363\u20132371. https:\/\/doi.org\/10.1093\/hmg\/4.12.2363","journal-title":"Hum Mol Genet"},{"key":"232_CR33","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1093\/hmg\/7.1.43","volume":"7","author":"M Cruts","year":"1998","unstructured":"Cruts M, van Duijn CM, Backhovens H et al (1998) Estimation of the genetic contribution of Presenilin-1 and -2 mutations in a population-based study of Presenile Alzheimer disease. Hum Mol Genet 7:43\u201351. https:\/\/doi.org\/10.1093\/hmg\/7.1.43","journal-title":"Hum Mol Genet"},{"key":"232_CR34","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1002\/humu.22117","volume":"33","author":"M Cruts","year":"2012","unstructured":"Cruts M, Theuns J, Van Broeckhoven C (2012) Locus-specific mutation databases for neurodegenerative brain diseases. Hum Mutat 33:1340\u20131344. https:\/\/doi.org\/10.1002\/humu.22117","journal-title":"Hum Mutat"},{"key":"232_CR35","doi-asserted-by":"publisher","first-page":"20117","DOI":"10.1074\/jbc.M213107200","volume":"278","author":"AS Crystal","year":"2003","unstructured":"Crystal AS, Morais VA, Pierson TC et al (2003) Membrane topology of \u03b3-secretase component PEN-2. J Biol Chem 278:20117\u201320123. https:\/\/doi.org\/10.1074\/jbc.M213107200","journal-title":"J Biol Chem"},{"key":"232_CR36","doi-asserted-by":"publisher","first-page":"15132","DOI":"10.18632\/oncotarget.23738","volume":"9","author":"MH Dai","year":"2018","unstructured":"Dai MH, Zheng H, Zeng LD, Zhang Y (2018) The genes associated with early-onset Alzheimer\u2019s disease. Oncotarget 9:15132\u201315143. https:\/\/doi.org\/10.18632\/oncotarget.23738","journal-title":"Oncotarget"},{"key":"232_CR37","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1093\/hmg\/8.8.1529","volume":"8","author":"C De Jonghe","year":"1999","unstructured":"De Jonghe C, MarcCruts REA et al (1999) Aberrant splicing in the Presenilin-1 intron 4 mutation causes Presenile Alzheimer\u2019s disease by increased a 42 secretion. Hum Mol Genet 8:1529\u20131540. https:\/\/doi.org\/10.1093\/hmg\/8.8.1529","journal-title":"Hum Mol Genet"},{"key":"232_CR38","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/s0896-6273(03)00205-8","volume":"38","author":"B De Strooper","year":"2003","unstructured":"De Strooper B (2003) Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-secretase complex. Neuron 38:9\u201312. https:\/\/doi.org\/10.1016\/s0896-6273(03)00205-8","journal-title":"Neuron"},{"key":"232_CR39","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1146\/annurev-cellbio-100109-104117","volume":"26","author":"B De Strooper","year":"2010","unstructured":"De Strooper B, Annaert W (2010) Novel research horizons for presenilins and \u03b3-secretases in cell biology and disease. Annu Rev Cell Dev Biol 26:235\u2013260. https:\/\/doi.org\/10.1146\/annurev-cellbio-100109-104117","journal-title":"Annu Rev Cell Dev Biol"},{"key":"232_CR40","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/S0014-5793(96)01142-8","volume":"397","author":"G Deng","year":"1996","unstructured":"Deng G, Pike CJ, Cotman CW (1996) Alzheimer-associated presenilin-2 confers increased sensitivity to poptosis in PC12 cells. FEBS Lett 397:50\u201354. https:\/\/doi.org\/10.1016\/S0014-5793(96)01142-8","journal-title":"FEBS Lett"},{"key":"232_CR41","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1001\/archneur.57.10.1454","volume":"57","author":"G Devi","year":"2000","unstructured":"Devi G, Fotiou A, Jyrinji D et al (2000) Novel Presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease. Arch Neurol 57:1454\u20131457. https:\/\/doi.org\/10.1001\/archneur.57.10.1454","journal-title":"Arch Neurol"},{"key":"232_CR42","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0070-2153(08)60381-6","volume":"43","author":"H Dierick","year":"1998","unstructured":"Dierick H, Bejsovec A (1998) 5 cellular mechanisms of wingless\/Wnt signal transduction. Curr Top Dev Biol 43:153\u2013190. https:\/\/doi.org\/10.1016\/S0070-2153(08)60381-6","journal-title":"Curr Top Dev Biol"},{"key":"232_CR43","doi-asserted-by":"publisher","first-page":"1481.e7","DOI":"10.1016\/j.neurobiolaging.2011.12.007","volume":"33","author":"V Dobricic","year":"2012","unstructured":"Dobricic V, Stefanova E, Jankovic M et al (2012) Genetic testing in familial and young-onset Alzheimer\u2019s disease: Mutation spectrum in a Serbian cohort. Neurobiol Aging 33:1481.e7\u20131481.e12. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2011.12.007","journal-title":"Neurobiol Aging"},{"key":"232_CR44","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.cell.2011.05.034","volume":"145","author":"R Dolmetsch","year":"2011","unstructured":"Dolmetsch R, Geschwind DH (2011) The human brain in a dish: the promise of iPSC-derived neurons. Cell 145:831\u2013834. https:\/\/doi.org\/10.1016\/j.cell.2011.05.034","journal-title":"Cell"},{"key":"232_CR45","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1586\/14737175.7.7.887","volume":"7","author":"R Dosunmu","year":"2007","unstructured":"Dosunmu R, Wu J, Basha MR, Zawia NH (2007) Environmental and dietary risk factors in Alzheimer\u2019s disease. Expert Rev Neurother 7:887\u2013900","journal-title":"Expert Rev Neurother"},{"key":"232_CR46","doi-asserted-by":"publisher","first-page":"132","DOI":"10.2174\/156720508783954695","volume":"5","author":"D Dries","year":"2008","unstructured":"Dries D, Yu G (2008) Assembly, maturation, and trafficking of the \u03b3-secretase complex in Alzheimers disease. Curr Alzheimer Res 5:132\u2013146. https:\/\/doi.org\/10.2174\/156720508783954695","journal-title":"Curr Alzheimer Res"},{"key":"232_CR47","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/383710a0","volume":"383","author":"K Duff","year":"1996","unstructured":"Duff K, Eckman C, Zehr C et al (1996) Increased amyloid-\u03b242(43) in brains of mice expressing mutant presenilin 1. Nature 383:710\u2013713. https:\/\/doi.org\/10.1038\/383710a0","journal-title":"Nature"},{"key":"232_CR48","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1136\/jmg.35.8.672","volume":"35","author":"C Dumanchin","year":"1998","unstructured":"Dumanchin C, Brice A, Campion D et al (1998) De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer\u2019s disease cases. J Med Genet 35:672\u2013673. https:\/\/doi.org\/10.1136\/jmg.35.8.672","journal-title":"J Med Genet"},{"key":"232_CR49","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.neuroscience.2014.03.052","volume":"269","author":"N El Kadmiri","year":"2014","unstructured":"El Kadmiri N, Zaid N, Zaid Y et al (2014) Novel presenilin mutations within Moroccan patients with early-onset Alzheimer\u2019s disease. Neuroscience 269:215\u2013222. https:\/\/doi.org\/10.1016\/j.neuroscience.2014.03.052","journal-title":"Neuroscience"},{"key":"232_CR50","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1212\/01.WNL.0000278386.00035.21","volume":"70","author":"N Ertekin-Taner","year":"2008","unstructured":"Ertekin-Taner N, Younkin LH, Yager DM et al (2008) Plasma amyloid beta protein is elevated in late-onset Alzheimer disease families. Neurology 70:596\u2013606. https:\/\/doi.org\/10.1212\/01.WNL.0000278386.00035.21","journal-title":"Neurology"},{"key":"232_CR51","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1001\/archneur.60.8.1149","volume":"60","author":"M Ezquerra","year":"2003","unstructured":"Ezquerra M, Lle\u00f3 A, Castellv\u00ed M et al (2003) A novel mutation in the PSEN2 gene (T430M) associated with variable expression in a family with early-onset Alzheimer disease. Arch Neurol 60:1149\u20131151. https:\/\/doi.org\/10.1001\/archneur.60.8.1149","journal-title":"Arch Neurol"},{"key":"232_CR52","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1212\/WNL.54.10.2006","volume":"54","author":"U Finckh","year":"2000","unstructured":"Finckh U, Alberici A, Antoniazzi M et al (2000a) Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I. Neurology 54:2006\u20132008. https:\/\/doi.org\/10.1212\/WNL.54.10.2006","journal-title":"Neurology"},{"key":"232_CR53","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1086\/302702","volume":"66","author":"U Finckh","year":"2000","unstructured":"Finckh U, M\u00fcller-Thomsen T, Mann U et al (2000b) High prevalence of pathogenic mutations patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet 66:110\u2013117. https:\/\/doi.org\/10.1086\/302702","journal-title":"Am J Hum Genet"},{"key":"232_CR54","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s10048-005-0211-x","volume":"6","author":"U Finckh","year":"2005","unstructured":"Finckh U, Kuschel C, Anagnostouli M et al (2005) Novel mutations and repeated findings of mutations in familial Alzheimer disease. Neurogenetics 6:85\u201389. https:\/\/doi.org\/10.1007\/s10048-005-0211-x","journal-title":"Neurogenetics"},{"key":"232_CR55","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0304-3940(97)00603-4","volume":"234","author":"C Forsell","year":"1997","unstructured":"Forsell C, Froelich S, Axelman K et al (1997) A novel pathogenic mutation (Leu262Phe) found in the presenilin 1 gene in early-onset Alzheimer\u2019s disease. Neurosci Lett 234:3\u20136. https:\/\/doi.org\/10.1016\/S0304-3940(97)00603-4","journal-title":"Neurosci Lett"},{"key":"232_CR56","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/s1534-5807(02)00189-2","volume":"3","author":"R Francis","year":"2002","unstructured":"Francis R, McGrath G, Zhang J et al (2002) aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell 3:85\u201397. https:\/\/doi.org\/10.1016\/s1534-5807(02)00189-2","journal-title":"Dev Cell"},{"key":"232_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0925-4439(00)00028-4","volume":"1502","author":"PE Fraser","year":"2000","unstructured":"Fraser PE, Yang DS, Yu G et al (2000) Presenilin structure, function and role in Alzheimer disease. Biochim Biophys Acta 1502:1\u201315. https:\/\/doi.org\/10.1016\/s0925-4439(00)00028-4","journal-title":"Biochim Biophys Acta"},{"key":"232_CR58","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s10072-009-0132-9","volume":"31","author":"M Gallo","year":"2010","unstructured":"Gallo M, Tomaino C, Puccio G et al (2010) Novel MAPT Val75Ala mutation and PSEN2 Arg62Hys in two siblings with frontotemporal dementia. Neurol Sci 31:65\u201370. https:\/\/doi.org\/10.1007\/s10072-009-0132-9","journal-title":"Neurol Sci"},{"key":"232_CR59","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1001\/archpsyc.63.2.168","volume":"63","author":"M Gatz","year":"2006","unstructured":"Gatz M, Reynolds CA, Fratiglioni L et al (2006) Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry 63:168\u2013174. https:\/\/doi.org\/10.1001\/archpsyc.63.2.168","journal-title":"Arch Gen Psychiatry"},{"key":"232_CR60","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.nbd.2004.10.016","volume":"18","author":"M Giacomello","year":"2005","unstructured":"Giacomello M, Barbiero L, Zatti G et al (2005) Reduction of Ca2+ stores and capacitative Ca2+ entry is associated with the familial Alzheimer\u2019s disease presenilin-2 T122R mutation and anticipates the onset of dementia. Neurobiol Dis 18:638\u2013648. https:\/\/doi.org\/10.1016\/j.nbd.2004.10.016","journal-title":"Neurobiol Dis"},{"key":"232_CR61","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1002\/ana.410410618","volume":"41","author":"T G\u00f3mez-Isla","year":"1997","unstructured":"G\u00f3mez-Isla T, Wasco W, Pettingell WP et al (1997) A novel presenilin-1 mutation: increased \u03b2-amyloid and neurofibrillary changes. Ann Neurol 41:809\u2013813. https:\/\/doi.org\/10.1002\/ana.410410618","journal-title":"Ann Neurol"},{"key":"232_CR62","doi-asserted-by":"publisher","first-page":"7374","DOI":"10.1074\/jbc.M209499200","volume":"278","author":"Y Gu","year":"2003","unstructured":"Gu Y, Chen F, Sanjo N et al (2003) APH-1 interacts with mature and immature forms of presenilins and Nicastrin and may play a role in maturation of Presenilin\u00b7Nicastrin complexes. J Biol Chem 278:7374\u20137380. https:\/\/doi.org\/10.1074\/jbc.M209499200","journal-title":"J Biol Chem"},{"key":"232_CR63","doi-asserted-by":"publisher","first-page":"31329","DOI":"10.1074\/jbc.M401548200","volume":"279","author":"Y Gu","year":"2004","unstructured":"Gu Y, Sanjo N, Chen F et al (2004) The Presenilin proteins are components of multiple membrane-bound complexes that have different biological activities. J Biol Chem 279:31329\u201331336. https:\/\/doi.org\/10.1074\/jbc.M401548200","journal-title":"J Biol Chem"},{"key":"232_CR64","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.neurobiolaging.2008.06.012","volume":"31","author":"RJ Guerreiro","year":"2010","unstructured":"Guerreiro RJ, Baquero M, Blesa R et al (2010) Genetic screening of Alzheimer\u2019s disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging 31:725\u2013731. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2008.06.012","journal-title":"Neurobiol Aging"},{"issue":"5580","key":"232_CR65","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy J, Selkoe DJ (2002a) The amyloid hypothesis of Alzheimer\u2019s disease: progress and problems on the road to therapeutics. Science 297(5580):353\u2013356. https:\/\/doi.org\/10.1126\/science.1072994","journal-title":"Science"},{"issue":"5580","key":"232_CR66","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy J, Selkoe DJ (2002b) The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics. Science 297(5580):353\u2013356. https:\/\/doi.org\/10.1126\/science.1072994","journal-title":"Science"},{"key":"232_CR67","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1111\/jphp.13132","volume":"71","author":"S Harilal","year":"2019","unstructured":"Harilal S, Jose J, Parambi DGT et al (2019) Advancements in nanotherapeutics for Alzheimer\u2019s disease: current perspectives. J Pharm Pharmacol 71:1370\u20131383. https:\/\/doi.org\/10.1111\/jphp.13132","journal-title":"J Pharm Pharmacol"},{"key":"232_CR68","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1136\/jnnp.64.1.44","volume":"64","author":"RJ Harvey","year":"1998","unstructured":"Harvey RJ, Ellison D, Hardy J et al (1998) Chromosome 14 familial Alzheimer\u2019s disease: the clinical and neuropathological characteristics of a family with a leucine\u2192serine (L250S) substitution at codon 250 of the presenilin 1 gene. J Neurol Neurosurg Psychiatry 64:44\u201349. https:\/\/doi.org\/10.1136\/jnnp.64.1.44","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"232_CR69","doi-asserted-by":"publisher","first-page":"22350","DOI":"10.1074\/jbc.M110.116962","volume":"285","author":"EA Heilig","year":"2010","unstructured":"Heilig EA, Xia W, Shen J, Kelleher RJ (2010) A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of \u03b3-secretase activity. J Biol Chem 285:22350\u201322359. https:\/\/doi.org\/10.1074\/jbc.M110.116962","journal-title":"J Biol Chem"},{"key":"232_CR70","doi-asserted-by":"publisher","first-page":"11606","DOI":"10.1523\/JNEUROSCI.0954-13.2013","volume":"33","author":"EA Heilig","year":"2013","unstructured":"Heilig EA, Gutti U, Tai T et al (2013) Trans-dominant negative effects of pathogenic PSEN1 mutations on \u03b3-secretase activity and A\u03b2 production. J Neurosci 33:11606\u201311617. https:\/\/doi.org\/10.1523\/JNEUROSCI.0954-13.2013","journal-title":"J Neurosci"},{"key":"232_CR71","doi-asserted-by":"publisher","first-page":"4393","DOI":"10.1021\/bi500489j","volume":"53","author":"O Holmes","year":"2014","unstructured":"Holmes O, Paturi S, Selkoe DJ, Wolfe MS (2014) Pen-2 is essential for \u03b3-secretase complex stability and trafficking but partially dispensable for endoproteolysis. Biochemistry 53:4393\u20134406. https:\/\/doi.org\/10.1021\/bi500489j","journal-title":"Biochemistry"},{"key":"232_CR72","doi-asserted-by":"publisher","first-page":"8255","DOI":"10.1007\/s12035-019-01660-3","volume":"58","author":"MF Hossain","year":"2019","unstructured":"Hossain MF, Uddin MS, Uddin GMS et al (2019) Melatonin in Alzheimer\u2019s disease: a latent endogenous regulator of neurogenesis to mitigate Alzheimer\u2019s neuropathology. Mol Neurobiol 58:8255\u20138276. https:\/\/doi.org\/10.1007\/s12035-019-01660-3","journal-title":"Mol Neurobiol"},{"key":"232_CR73","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1002\/ana.410400614","volume":"40","author":"M Ikeda","year":"1996","unstructured":"Ikeda M, Sharma V, Mark Sumi S et al (1996) The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients. Ann Neurol 40:912\u2013917. https:\/\/doi.org\/10.1002\/ana.410400614","journal-title":"Ann Neurol"},{"key":"232_CR74","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/s0304-3940(97)13343-2","volume":"222","author":"NG Irving","year":"1997","unstructured":"Irving NG, Miller CC (1997) Tau phosphorylation in cells transfected with wild-type or an Alzheimer\u2019s disease mutant Presenilin 1. Neurosci Lett 222:71\u201374. https:\/\/doi.org\/10.1016\/s0304-3940(97)13343-2","journal-title":"Neurosci Lett"},{"key":"232_CR75","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1093\/brain\/awq033","volume":"133","author":"S Jayadev","year":"2010","unstructured":"Jayadev S, Leverenz JB, Steinbart E et al (2010) Alzheimer\u2019s disease phenotypes and genotypes associated with mutations in presenilin 2. Brain 133:1143\u20131154. https:\/\/doi.org\/10.1093\/brain\/awq033","journal-title":"Brain"},{"key":"232_CR76","doi-asserted-by":"publisher","first-page":"852","DOI":"10.2174\/15672050113109990155","volume":"10","author":"T Jiang","year":"2013","unstructured":"Jiang T, Yu J-T, Tian Y, Tan L (2013) Epidemiology and etiology of Alzheimer\u2019s disease: from genetic to non- genetic factors. Curr Alzheimer Res 10:852\u2013867. https:\/\/doi.org\/10.2174\/15672050113109990155","journal-title":"Curr Alzheimer Res"},{"key":"232_CR77","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1111\/j.1399-0004.1996.tb02375.x","volume":"50","author":"P J\u00f8rgensen","year":"2008","unstructured":"J\u00f8rgensen P, Bus C, Pallisgaard N et al (2008) Familial Alzheimer\u2019s disease co-segregates with a Met 146 Ile substitution in presenilin-1. Clin Genet 50:281\u2013286. https:\/\/doi.org\/10.1111\/j.1399-0004.1996.tb02375.x","journal-title":"Clin Genet"},{"key":"232_CR78","doi-asserted-by":"publisher","first-page":"3506","DOI":"10.2174\/1381612825666191011102444","volume":"25","author":"MT Kabir","year":"2019","unstructured":"Kabir MT, Abu Sufian M, Uddin MS et al (2019a) NMDA receptor antagonists: repositioning of memantine as multitargeting agent for Alzheimer\u2019s therapy. Curr Pharm Des 25:3506\u20133518. https:\/\/doi.org\/10.2174\/1381612825666191011102444","journal-title":"Curr Pharm Des"},{"key":"232_CR79","doi-asserted-by":"publisher","first-page":"3519","DOI":"10.2174\/1381612825666191008103141","volume":"25","author":"MT Kabir","year":"2019","unstructured":"Kabir MT, Uddin MS, Begum MM et al (2019b) Cholinesterase inhibitors for Alzheimer\u2019s disease: multitargeting strategy based on anti-Alzheimer\u2019s drugs repositioning. Curr Pharm Des 25:3519\u20133535. https:\/\/doi.org\/10.2174\/1381612825666191008103141","journal-title":"Curr Pharm Des"},{"key":"232_CR80","doi-asserted-by":"publisher","first-page":"3272","DOI":"10.3390\/IJMS21093272","volume":"21","author":"MT Kabir","year":"2020","unstructured":"Kabir MT, Uddin MS, Al Mamun A et al (2020a) Combination drug therapy for the Management of Alzheimer\u2019s disease. Int J Mol Sci 21:3272. https:\/\/doi.org\/10.3390\/IJMS21093272","journal-title":"Int J Mol Sci"},{"issue":"13","key":"232_CR81","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.2174\/1568026620666200422105156","volume":"20","author":"MT Kabir","year":"2020","unstructured":"Kabir MT, Uddin MS, Mathew B et al (2020b) Emerging promise of immunotherapy for Alzheimer\u2019s disease: a new hope for the development of Alzheimer\u2019s vaccine. Curr Top Med Chem 20(13):1214\u20131234. https:\/\/doi.org\/10.2174\/1568026620666200422105156","journal-title":"Curr Top Med Chem"},{"key":"232_CR82","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/0304-3940(96)12587-8","volume":"208","author":"K Kamino","year":"1996","unstructured":"Kamino K, Sato S, Sakaki Y et al (1996) Three different mutations of presenilin 1 gene in early-onset Alzheimer\u2019s disease families. Neurosci Lett 208:195\u2013198. https:\/\/doi.org\/10.1016\/0304-3940(96)12587-8","journal-title":"Neurosci Lett"},{"key":"232_CR83","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/nrd3505","volume":"10","author":"E Karran","year":"2011","unstructured":"Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer\u2019s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10:698\u2013712. https:\/\/doi.org\/10.1038\/nrd3505","journal-title":"Nat Rev Drug Discov"},{"key":"232_CR84","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1074\/jbc.M412404200","volume":"280","author":"S-H Kim","year":"2005","unstructured":"Kim S-H, Sisodia SS (2005a) A sequence within the first transmembrane domain of PEN-2 is critical for PEN-2-mediated endoproteolysis of Presenilin 1. J Biol Chem 280:1992\u20132001. https:\/\/doi.org\/10.1074\/jbc.M412404200","journal-title":"J Biol Chem"},{"key":"232_CR85","doi-asserted-by":"publisher","first-page":"41953","DOI":"10.1074\/jbc.M509070200","volume":"280","author":"S-H Kim","year":"2005","unstructured":"Kim S-H, Sisodia SS (2005b) Evidence that the \u201cNF\u201d motif in transmembrane domain 4 of Presenilin 1 is critical for binding with PEN-2. J Biol Chem 280:41953\u201341966. https:\/\/doi.org\/10.1074\/jbc.M509070200","journal-title":"J Biol Chem"},{"key":"232_CR86","doi-asserted-by":"publisher","first-page":"11006","DOI":"10.1074\/jbc.272.17.11006","volume":"272","author":"T-W Kim","year":"1997","unstructured":"Kim T-W, Pettingell WH, Hallmark OG et al (1997) Endoproteolytic cleavage and proteasomal degradation of Presenilin 2 in transfected cells. J Biol Chem 272:11006\u201311010. https:\/\/doi.org\/10.1074\/jbc.272.17.11006","journal-title":"J Biol Chem"},{"key":"232_CR87","first-page":"57","volume":"37","author":"A Kowalska","year":"1999","unstructured":"Kowalska A, Forsell C, Florczak J et al (1999) A Polish pedigree with Alzheimer\u2019s disease determined by a novel mutation in exon 12 of the presenilin 1 gene: clinical and molecular characterization. Folia Neuropathol 37:57\u201361","journal-title":"Folia Neuropathol"},{"key":"232_CR88","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1097\/00001756-199704140-00043","volume":"8","author":"JBJ Kwok","year":"1997","unstructured":"Kwok JBJ, Taddei K, Hallupp M et al (1997) Two novel (M233T and \u03c1278T) presenilin-1 mutations in early-onset Alzheimer\u02bcs disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype. Neuroreport 8:1537\u20131542. https:\/\/doi.org\/10.1097\/00001756-199704140-00043","journal-title":"Neuroreport"},{"key":"232_CR89","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/nrn960","volume":"3","author":"FM LaFerla","year":"2002","unstructured":"LaFerla FM (2002) Calcium dyshomeostasis and intracellular signalling in alzheimer\u2019s disease. Nat Rev Neurosci 3:862\u2013872. https:\/\/doi.org\/10.1038\/nrn960","journal-title":"Nat Rev Neurosci"},{"key":"232_CR90","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s100480050044","volume":"1","author":"JI Lao","year":"1998","unstructured":"Lao JI, Beyer K, Fern\u00e1ndez-Novoa L, Cacabelos R (1998) A novel mutation in the predicted TM2 domain of the presenilin 2 gene in a Spanish patient with late-onset Alzheimer\u2019s disease. Neurogenetics 1:293\u2013296. https:\/\/doi.org\/10.1007\/s100480050044","journal-title":"Neurogenetics"},{"key":"232_CR91","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.yebeh.2011.03.022","volume":"21","author":"AJ Larner","year":"2011","unstructured":"Larner AJ (2011) Presenilin-1 mutation Alzheimer\u2019s disease: a genetic epilepsy syndrome? Epilepsy Behav 21:20\u201322. https:\/\/doi.org\/10.1016\/j.yebeh.2011.03.022","journal-title":"Epilepsy Behav"},{"key":"232_CR92","doi-asserted-by":"publisher","first-page":"7513","DOI":"10.1523\/jneurosci.16-23-07513.1996","volume":"16","author":"MK Lee","year":"1996","unstructured":"Lee MK, Slunt HH, Martin LJ et al (1996) Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues. J Neurosci 16:7513\u20137525. https:\/\/doi.org\/10.1523\/jneurosci.16-23-07513.1996","journal-title":"J Neurosci"},{"key":"232_CR93","doi-asserted-by":"publisher","first-page":"45013","DOI":"10.1074\/jbc.M208164200","volume":"277","author":"S-F Lee","year":"2002","unstructured":"Lee S-F, Shah S, Li H et al (2002) Mammalian APH-1 interacts with Presenilin and Nicastrin and is required for intramembrane proteolysis of amyloid-\u03b2 precursor protein and notch. J Biol Chem 277:45013\u201345019. https:\/\/doi.org\/10.1074\/jbc.M208164200","journal-title":"J Biol Chem"},{"key":"232_CR94","doi-asserted-by":"publisher","first-page":"4144","DOI":"10.1074\/jbc.M309745200","volume":"279","author":"S-F Lee","year":"2004","unstructured":"Lee S-F, Shah S, Yu C et al (2004) A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex. J Biol Chem 279:4144\u20134152. https:\/\/doi.org\/10.1074\/jbc.M309745200","journal-title":"J Biol Chem"},{"key":"232_CR95","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/j.cell.2010.05.008","volume":"141","author":"JH Lee","year":"2010","unstructured":"Lee JH, Yu WH, Kumar A et al (2010) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:1146\u20131158. https:\/\/doi.org\/10.1016\/j.cell.2010.05.008","journal-title":"Cell"},{"key":"232_CR96","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1002\/mgg3.85","volume":"2","author":"JH Lee","year":"2014","unstructured":"Lee JH, Kahn A, Cheng R et al (2014) Disease-related mutations among Caribbean Hispanics with familial dementia. Mol Genet Genomic Med 2:430\u2013437. https:\/\/doi.org\/10.1002\/mgg3.85","journal-title":"Mol Genet Genomic Med"},{"key":"232_CR97","doi-asserted-by":"publisher","first-page":"8590","DOI":"10.1073\/pnas.97.15.8590","volume":"97","author":"MA Leissring","year":"2000","unstructured":"Leissring MA, Yamasaki TR, Wasco W et al (2000) Calsenilin reverses presenilin-mediated enhancement of calcium signaling. Proc Natl Acad Sci U S A 97:8590\u20138593. https:\/\/doi.org\/10.1073\/pnas.97.15.8590","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5226","key":"232_CR98","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1126\/science.7638622","volume":"269","author":"E Levy-Lahad","year":"1995","unstructured":"Levy-Lahad E, Wasco W, Poorkaj P et al (1995a) Candidate gene for the chromosome 1 familial Alzheimer\u2019s disease locus. Science 269(5226):973\u2013977. https:\/\/doi.org\/10.1126\/science.7638622","journal-title":"Science"},{"issue":"5226","key":"232_CR99","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1126\/science.7638621","volume":"269","author":"E Levy-Lahad","year":"1995","unstructured":"Levy-Lahad E, Wijsman EM, Nemens E et al (1995b) A familial Alzheimer\u2019s disease locus on chromosome I. Science 269(5226):970\u2013973. https:\/\/doi.org\/10.1126\/science.7638621","journal-title":"Science"},{"key":"232_CR100","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1086\/509900","volume":"79","author":"D Li","year":"2006","unstructured":"Li D, Parks SB, Kushner JD et al (2006) Mutations of Presenilin genes in dilated cardiomyopathy and heart failure. Am J Hum Genet 79:1030\u20131039. https:\/\/doi.org\/10.1086\/509900","journal-title":"Am J Hum Genet"},{"key":"232_CR101","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.str.2013.09.018","volume":"22","author":"Y Li","year":"2014","unstructured":"Li Y, Lu SH-J, Tsai C-J et al (2014) Structural interactions between inhibitor and substrate docking sites give insight into mechanisms of human PS1 complexes. Structure 22:125\u2013135. https:\/\/doi.org\/10.1016\/j.str.2013.09.018","journal-title":"Structure"},{"key":"232_CR102","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1111\/j.1468-1331.2008.02256.x","volume":"15","author":"SG Lindquist","year":"2008","unstructured":"Lindquist SG, Hasholt L, Bahl JMC et al (2008) A novel presenilin 2 mutation (V393M) in early-onset dementia with profound language impairment. Eur J Neurol 15:1135\u20131139. https:\/\/doi.org\/10.1111\/j.1468-1331.2008.02256.x","journal-title":"Eur J Neurol"},{"key":"232_CR103","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1111\/j.1399-0004.2009.01191.x","volume":"76","author":"SG Lindquist","year":"2009","unstructured":"Lindquist SG, Schwartz M, Batbayli M et al (2009) Genetic testing in familial AD and FTD: mutation and phenotype spectrum in a Danish cohort. Clin Genet 76:205\u2013209. https:\/\/doi.org\/10.1111\/j.1399-0004.2009.01191.x","journal-title":"Clin Genet"},{"key":"232_CR104","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1212\/wnl.57.10.1926","volume":"57","author":"A Lle\u00f3","year":"2001","unstructured":"Lle\u00f3 A, Blesa R, Gendre J et al (2001) A novel presenilin 2 gene mutation (D439A) in a patient with early-onset Alzheimer\u2019s disease. Neurology 57:1926\u20131928. https:\/\/doi.org\/10.1212\/wnl.57.10.1926","journal-title":"Neurology"},{"key":"232_CR105","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1001\/archneur.59.11.1759","volume":"59","author":"A Lle\u00f3","year":"2002","unstructured":"Lle\u00f3 A, Blesa R, Queralt R et al (2002a) Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch Neurol 59:1759\u20131763. https:\/\/doi.org\/10.1001\/archneur.59.11.1759","journal-title":"Arch Neurol"},{"key":"232_CR106","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/S0304-3940(01)02499-5","volume":"318","author":"A Lle\u00f3","year":"2002","unstructured":"Lle\u00f3 A, Castellv\u00ed M, Blesa R, Oliva R (2002b) Uncommon polymorphism in the presenilin genes in human familial Alzheimer\u2019s disease: not to be mistaken with a pathogenic mutation. Neurosci Lett 318:166\u2013168. https:\/\/doi.org\/10.1016\/S0304-3940(01)02499-5","journal-title":"Neurosci Lett"},{"key":"232_CR107","doi-asserted-by":"publisher","first-page":"1850.e17","DOI":"10.1016\/j.neurobiolaging.2012.02.020","volume":"33","author":"E Lohmann","year":"2012","unstructured":"Lohmann E, Guerreiro RJ, Erginel-Unaltuna N et al (2012) Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients. Neurobiol Aging 33:1850.e17\u20131850.e27. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2012.02.020","journal-title":"Neurobiol Aging"},{"key":"232_CR108","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1096\/fj.06-6380com","volume":"21","author":"Y Lu","year":"2007","unstructured":"Lu Y, Lv Y, Ye Y et al (2007) A role for presenilin in post-stress regulation: effects of presenilin mutations on Ca2+ currents in Drosophila. FASEB J 21:2368\u20132378. https:\/\/doi.org\/10.1096\/fj.06-6380com","journal-title":"FASEB J"},{"key":"232_CR109","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1111\/jnc.12016","volume":"123","author":"G Mao","year":"2012","unstructured":"Mao G, Cui M-Z, Li T et al (2012) Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both \u03b3-secretase assembly and substrate recruitment. J Neurochem 123:837\u2013844. https:\/\/doi.org\/10.1111\/jnc.12016","journal-title":"J Neurochem"},{"key":"232_CR110","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/jnen\/63.3.199","volume":"63","author":"G Marcon","year":"2004","unstructured":"Marcon G, Giaccone G, Cupidi C et al (2004) Neuropathological and clinical phenotype of an Italian Alzheimer family with M239V mutation of Presenilin 2 gene. J Neuropathol Exp Neurol 63:199\u2013209. https:\/\/doi.org\/10.1093\/jnen\/63.3.199","journal-title":"J Neuropathol Exp Neurol"},{"key":"232_CR111","doi-asserted-by":"publisher","first-page":"509","DOI":"10.3233\/JAD-2009-0986","volume":"16","author":"G Marcon","year":"2009","unstructured":"Marcon G, Di Fede G, Giaccone G et al (2009) A novel italian presenilin 2 gene mutation with prevalent behavioral phenotype. J Alzheimers Dis 16:509\u2013511. https:\/\/doi.org\/10.3233\/JAD-2009-0986","journal-title":"J Alzheimers Dis"},{"key":"232_CR112","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1002\/ana.410440617","volume":"44","author":"KM Mattila","year":"1998","unstructured":"Mattila KM, Forsell C, Pirttila T et al (1998) The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer\u2019s disease. Ann Neurol 44:965\u2013967. https:\/\/doi.org\/10.1002\/ana.410440617","journal-title":"Ann Neurol"},{"key":"232_CR113","doi-asserted-by":"publisher","first-page":"629.e5","DOI":"10.1016\/j.neurobiolaging.2011.10.014","volume":"33","author":"B Meeus","year":"2012","unstructured":"Meeus B, Verstraeten A, Crosiers D et al (2012) DLB and PDD: a role for mutations in dementia and Parkinson disease genes. Neurobiol Aging 33:629.e5\u2013629.e18. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2011.10.014","journal-title":"Neurobiol Aging"},{"key":"232_CR114","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/0014-5793(96)00608-4","volume":"389","author":"M Mercken","year":"1996","unstructured":"Mercken M, Takahashi H, Honda T et al (1996) Characterization of human presenilin 1 using N-terminal specific monoclonal antibodies: evidence that Alzheimer mutations affect proteolytic processing. FEBS Lett 389:297\u2013303. https:\/\/doi.org\/10.1016\/0014-5793(96)00608-4","journal-title":"FEBS Lett"},{"key":"232_CR115","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3233\/JAD-140399","volume":"42","author":"U M\u00fcller","year":"2014","unstructured":"M\u00fcller U, Winter P, Bolender C, Nolte D (2014) Previously unrecognized missense mutation E126K of PSEN2 segregates with early onset Alzheimer\u2019s disease in a family. J Alzheimers Dis 42:109\u2013113. https:\/\/doi.org\/10.3233\/JAD-140399","journal-title":"J Alzheimers Dis"},{"key":"232_CR116","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/5526","volume":"5","author":"M Nishimura","year":"1999","unstructured":"Nishimura M, Yu G, Levesque G et al (1999a) Presenilin mutations associated with Alzheimer disease cause defective intracellular trafficking of \u03b2-catenin,a component of the presenilin protein complex. Nat Med 5:164\u2013169. https:\/\/doi.org\/10.1038\/5526","journal-title":"Nat Med"},{"key":"232_CR117","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1034\/j.1399-0004.1999.550401.x","volume":"55","author":"M Nishimura","year":"1999","unstructured":"Nishimura M, Yu G, St George-Hyslop PH (1999b) Biology of presenilins as causative molecules for Alzheimer disease. Clin Genet 55:219\u2013225. https:\/\/doi.org\/10.1034\/j.1399-0004.1999.550401.x","journal-title":"Clin Genet"},{"key":"232_CR118","doi-asserted-by":"publisher","first-page":"2420.e1","DOI":"10.1016\/j.neurobiolaging.2014.04.011","volume":"35","author":"F Niu","year":"2014","unstructured":"Niu F, Yu S, Zhang Z et al (2014) A novel mutation in the PSEN2 gene (N141Y) associated with early-onset autosomal dominant Alzheimer\u2019s disease in a Chinese Han family. Neurobiol Aging 35:2420.e1\u20132420.e5. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2014.04.011","journal-title":"Neurobiol Aging"},{"key":"232_CR119","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1002\/(sici)1098-1004(1999)13:3<256::aid-humu11>3.0.co;2-p","volume":"13","author":"MS Palmer","year":"1999","unstructured":"Palmer MS, Beck JA, Campbell TA et al (1999) Pathogenic presenilin 1 mutations (P436S & I143F) in early-onset Alzheimer\u2019s disease in the UK. Mutations in brief no. 223. Hum Mutat 13:256. https:\/\/doi.org\/10.1002\/(sici)1098-1004(1999)13:3<256::aid-humu11>3.0.co;2-p","journal-title":"Hum Mutat"},{"key":"232_CR120","doi-asserted-by":"publisher","first-page":"16298","DOI":"10.1074\/jbc.M109.000067","volume":"284","author":"R Pardossi-Piquard","year":"2009","unstructured":"Pardossi-Piquard R, Yang S-P, Kanemoto S et al (2009) APH1 polar transmembrane residues regulate the assembly and activity of Presenilin complexes. J Biol Chem 284:16298\u201316307. https:\/\/doi.org\/10.1074\/jbc.M109.000067","journal-title":"J Biol Chem"},{"key":"232_CR121","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/ana.10636","volume":"54","author":"P Pastor","year":"2003","unstructured":"Pastor P, Roe CM, Villegas A et al (2003) Apolipoprotein Eepsilon4 modifies Alzheimer\u2019s disease onset in an E280A PS1 kindred. Ann Neurol 54:163\u2013169. https:\/\/doi.org\/10.1002\/ana.10636","journal-title":"Ann Neurol"},{"key":"232_CR122","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1097\/00001756-199512000-00071","volume":"7","author":"J Perez-Tur","year":"1995","unstructured":"Perez-Tur J, Froelich S, Prihar G et al (1995) A mutation in Alzheimer\u2019s disease destroying a splice acceptor site in the presenilin-1 gene. Neuroreport 7:297\u2013301","journal-title":"Neuroreport"},{"key":"232_CR123","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1006\/NEUR.1996.0028","volume":"5","author":"J Perez-Tur","year":"1996","unstructured":"Perez-Tur J, Croxton R, Wright K et al (1996) A further Presenilin 1 mutation in the exon 8 cluster in familial Alzheimer\u2019s disease. Neurodegeneration 5:207\u2013212. https:\/\/doi.org\/10.1006\/NEUR.1996.0028","journal-title":"Neurodegeneration"},{"key":"232_CR124","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1212\/01.wnl.0000310643.53587.87","volume":"70","author":"P Piscopo","year":"2008","unstructured":"Piscopo P, Marcon G, Piras MR et al (2008) A novel PSEN2 mutation associated with a peculiar phenotype. Neurology 70:1549\u20131554. https:\/\/doi.org\/10.1212\/01.wnl.0000310643.53587.87","journal-title":"Neurology"},{"key":"232_CR125","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3233\/JAD-2010-1369","volume":"20","author":"P Piscopo","year":"2010","unstructured":"Piscopo P, Talarico G, Crestini A et al (2010) A novel mutation in the predicted TMIII domain of the PSEN2 gene in an Italian pedigree with atypical Alzheimer\u2019s disease. J Alzheimers Dis 20:43\u201347. https:\/\/doi.org\/10.3233\/JAD-2010-1369","journal-title":"J Alzheimers Dis"},{"key":"232_CR126","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1006\/nbdi.1997.0129","volume":"3","author":"MB Podlisny","year":"1997","unstructured":"Podlisny MB, Citron M, Amarante P et al (1997) Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue. Neurobiol Dis 3:325\u2013337. https:\/\/doi.org\/10.1006\/nbdi.1997.0129","journal-title":"Neurobiol Dis"},{"key":"232_CR127","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1002\/(SICI)1098-1004(1998)11:3<216::AID-HUMU6>3.0.CO;2-F","volume":"11","author":"P Poorkaj","year":"1998","unstructured":"Poorkaj P, Sharma V, Anderson L et al (1998) Missense mutations in the chromosome 14 familial Alzheimer\u2019s disease presenilin 1 gene. Hum Mutat 11:216\u2013221. https:\/\/doi.org\/10.1002\/(SICI)1098-1004(1998)11:3<216::AID-HUMU6>3.0.CO;2-F","journal-title":"Hum Mutat"},{"key":"232_CR128","doi-asserted-by":"publisher","first-page":"23255","DOI":"10.1074\/jbc.M401789200","volume":"279","author":"S Prokop","year":"2004","unstructured":"Prokop S, Shirotani K, Edbauer D et al (2004) Requirement of PEN-2 for stabilization of the Presenilin N-\/C-terminal fragment heterodimer within the \u03b3-secretase complex. J Biol Chem 279:23255\u201323261. https:\/\/doi.org\/10.1074\/jbc.M401789200","journal-title":"J Biol Chem"},{"key":"232_CR129","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.parkreldis.2009.06.007","volume":"15","author":"A Puschmann","year":"2009","unstructured":"Puschmann A, Ross OA, Vilari\u00f1o-G\u00fcell C et al (2009) A Swedish family with de novo \u03b1-synuclein A53T mutation: evidence for early cortical dysfunction. Parkinsonism Relat Disord 15:627\u2013632. https:\/\/doi.org\/10.1016\/j.parkreldis.2009.06.007","journal-title":"Parkinsonism Relat Disord"},{"key":"232_CR130","doi-asserted-by":"publisher","first-page":"772","DOI":"10.2174\/1381612826666200107142541","volume":"26","author":"MA Rahman","year":"2020","unstructured":"Rahman MA, Rahman MR, Zaman T et al (2020) Emerging potential of naturally occurring autophagy modulator against neurodegeneration. Curr Pharm Des 26:772\u2013779. https:\/\/doi.org\/10.2174\/1381612826666200107142541","journal-title":"Curr Pharm Des"},{"key":"232_CR131","first-page":"149","volume":"41","author":"MG Ramirez-Due\u00f1as","year":"1998","unstructured":"Ramirez-Due\u00f1as MG, Rogaeva EA, Leal CA et al (1998) A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with early onset Alzheimer disease. Ann Genet 41:149\u2013153","journal-title":"Ann Genet"},{"key":"232_CR132","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1074\/jbc.M113.512921","volume":"289","author":"Y Ran","year":"2014","unstructured":"Ran Y, Cruz PE, Ladd TB et al (2014) \u03b3-Secretase processing and effects of \u03b3-secretase inhibitors and modulators on long A\u03b2 peptides in cells. J Biol Chem 289:3276\u20133287. https:\/\/doi.org\/10.1074\/jbc.M113.512921","journal-title":"J Biol Chem"},{"key":"232_CR133","doi-asserted-by":"publisher","first-page":"369808","DOI":"10.1155\/2012\/369808","volume":"2012","author":"C Reitz","year":"2012","unstructured":"Reitz C (2012) Alzheimer\u2019s disease and the amyloid cascade hypothesis: a critical review. Int J Alzheimers Dis 2012:369808. https:\/\/doi.org\/10.1155\/2012\/369808","journal-title":"Int J Alzheimers Dis"},{"key":"232_CR134","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.bcp.2013.12.024","volume":"88","author":"C Reitz","year":"2014","unstructured":"Reitz C, Mayeux R (2014) Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol 88:640\u2013651. https:\/\/doi.org\/10.1016\/j.bcp.2013.12.024","journal-title":"Biochem Pharmacol"},{"key":"232_CR135","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1007\/s004390050288","volume":"98","author":"H Reznik-Wolf","year":"1996","unstructured":"Reznik-Wolf H, Treves TA, Davidson M et al (1996) A novel mutation of presenilin 1 in familial Alzheimer\u2019s disease in Israel detected by denaturing gradient gel electrophoresis. Hum Genet 98:700\u2013702. https:\/\/doi.org\/10.1007\/s004390050288","journal-title":"Hum Genet"},{"key":"232_CR136","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/sj.ejhg.5200160","volume":"6","author":"H Reznik-Wolf","year":"1998","unstructured":"Reznik-Wolf H, Treves T, Shabtai H et al (1998) Germline mutational analysis of presenilin 1 and APP genes in Jewish-Israeli individuals with familial or early-onset Alzheimer disease using denaturing gradient gel electrophoresis (DGGE). Eur J Hum Genet 6:176\u2013180. https:\/\/doi.org\/10.1038\/sj.ejhg.5200160","journal-title":"Eur J Hum Genet"},{"key":"232_CR137","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/376775a0","volume":"376","author":"EI Rogaev","year":"1995","unstructured":"Rogaev EI, Sherrington R, Rogaeva EA et al (1995) Familial Alzheimer\u2019s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer\u2019s disease type 3 gene. Nature 376:775\u2013778. https:\/\/doi.org\/10.1038\/376775a0","journal-title":"Nature"},{"key":"232_CR138","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1097\/00001756-199908020-00006","volume":"10","author":"I Romero","year":"1999","unstructured":"Romero I, J\u00f8rgensen P, Bolwig G et al (1999) A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer\u02bcs disease. Neuroreport 10:2255\u20132260. https:\/\/doi.org\/10.1097\/00001756-199908020-00006","journal-title":"Neuroreport"},{"key":"232_CR139","doi-asserted-by":"publisher","first-page":"99","DOI":"10.2217\/bmm.09.92","volume":"4","author":"NS Ryan","year":"2010","unstructured":"Ryan NS, Rossor MN (2010) Correlating familial Alzheimers disease gene mutations with clinical phenotype. Biomark Med 4:99\u2013112","journal-title":"Biomark Med"},{"key":"232_CR140","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1212\/WNL.0000000000000596","volume":"83","author":"DC Ryman","year":"2014","unstructured":"Ryman DC, Acosta-Baena N, Aisen PS et al (2014) Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology 83:253\u2013260. https:\/\/doi.org\/10.1212\/WNL.0000000000000596","journal-title":"Neurology"},{"key":"232_CR141","doi-asserted-by":"publisher","first-page":"2422.e13","DOI":"10.1016\/j.neurobiolaging.2014.04.026","volume":"35","author":"C Sassi","year":"2014","unstructured":"Sassi C, Guerreiro R, Gibbs R et al (2014) Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer\u2019s disease. Neurobiol Aging 35:2422.e13\u20132422.e16. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2014.04.026","journal-title":"Neurobiol Aging"},{"key":"232_CR142","doi-asserted-by":"publisher","first-page":"S91","DOI":"10.1002\/humu.1380110131","volume":"11","author":"S Sato","year":"1998","unstructured":"Sato S, Kamino K, Miki T et al (1998) Splicing mutation of presenilinl gene for earlyonset familial Alzheimer\u2019s disease. Hum Mutat 11:S91\u2013S94. https:\/\/doi.org\/10.1002\/humu.1380110131","journal-title":"Hum Mutat"},{"key":"232_CR143","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0896-6273(04)00182-5","volume":"42","author":"CA Saura","year":"2004","unstructured":"Saura CA, Choi SY, Beglopoulos V et al (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42:23\u201336. https:\/\/doi.org\/10.1016\/S0896-6273(04)00182-5","journal-title":"Neuron"},{"key":"232_CR144","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/nm0896-864","volume":"2","author":"D Scheuner","year":"1996","unstructured":"Scheuner D, Eckman C, Jensen M et al (1996) Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer\u2019s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer\u2019s disease. Nat Med 2:864\u2013870","journal-title":"Nat Med"},{"key":"232_CR145","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1152\/physrev.2001.81.2.741","volume":"81","author":"DJ Selkoe","year":"2001","unstructured":"Selkoe DJ (2001) Alzheimer\u2019s disease: genes, proteins, and therapy. Physiol Rev 81:741\u2013766","journal-title":"Physiol Rev"},{"key":"232_CR146","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Mol Med 8:595\u2013608. https:\/\/doi.org\/10.15252\/emmm.201606210","journal-title":"EMBO Mol Med"},{"key":"232_CR147","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1126\/science.1171176","volume":"324","author":"L Serneels","year":"2009","unstructured":"Serneels L, Van Biervliet J, Craessaerts K et al (2009) Gamma-secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer\u2019s disease. Science 324:639\u2013642. https:\/\/doi.org\/10.1126\/science.1171176","journal-title":"Science"},{"key":"232_CR148","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.cell.2005.05.022","volume":"122","author":"S Shah","year":"2005","unstructured":"Shah S, Lee S-F, Tabuchi K et al (2005) Nicastrin functions as a \u03b3-secretase-substrate receptor. Cell 122:435\u2013447. https:\/\/doi.org\/10.1016\/j.cell.2005.05.022","journal-title":"Cell"},{"key":"232_CR149","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1073\/pnas.0608332104","volume":"104","author":"J Shen","year":"2007","unstructured":"Shen J, Kelleher RJ (2007) The presenilin hypothesis of Alzheimer\u2019s disease: evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci U S A 104:403\u2013409","journal-title":"Proc Natl Acad Sci U S A"},{"key":"232_CR150","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/s0092-8674(00)80244-5","volume":"89","author":"J Shen","year":"1997","unstructured":"Shen J, Bronson RT, Chen DF et al (1997) Skeletal and CNS defects in Presenilin-1-deficient mice. Cell 89:629\u2013639. https:\/\/doi.org\/10.1016\/s0092-8674(00)80244-5","journal-title":"Cell"},{"key":"232_CR151","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/375754a0","volume":"375","author":"R Sherrington","year":"1995","unstructured":"Sherrington R, Rogaev EI, Liang Y et al (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer\u2019s disease. Nature 375:754\u2013760. https:\/\/doi.org\/10.1038\/375754a0","journal-title":"Nature"},{"key":"232_CR152","doi-asserted-by":"publisher","first-page":"16474","DOI":"10.1074\/jbc.C300095200","volume":"278","author":"K Shirotani","year":"2003","unstructured":"Shirotani K, Edbauer D, Capell A et al (2003) \u03b3-Secretase activity is associated with a conformational change of nicastrin. J Biol Chem 278:16474\u201316477. https:\/\/doi.org\/10.1074\/jbc.C300095200","journal-title":"J Biol Chem"},{"key":"232_CR153","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1093\/brain\/awh179","volume":"127","author":"K Sleegers","year":"2004","unstructured":"Sleegers K, Roks G, Theuns J et al (2004) Familial clustering and genetic risk for dementia in a genetically isolated Dutch population. Brain 127:1641\u20131649. https:\/\/doi.org\/10.1093\/brain\/awh179","journal-title":"Brain"},{"key":"232_CR154","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1097\/00001756-199902250-00011","volume":"10","author":"MJ Smith","year":"1999","unstructured":"Smith MJ, Gardner RJM, Knight MA et al (1999) Early-onset Alzheimer\u2019s disease caused by a novel mutation at codon 219 of the presenilin-1 gene. Neuroreport 10:503\u2013507. https:\/\/doi.org\/10.1097\/00001756-199902250-00011","journal-title":"Neuroreport"},{"key":"232_CR155","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.cell.2011.06.019","volume":"146","author":"F Soldner","year":"2011","unstructured":"Soldner F, Lagani\u00e8re J, Cheng AW et al (2011) Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146:318\u2013331. https:\/\/doi.org\/10.1016\/j.cell.2011.06.019","journal-title":"Cell"},{"key":"232_CR156","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1083\/jcb.200609180","volume":"176","author":"D Spasic","year":"2007","unstructured":"Spasic D, Raemaekers T, Dillen K et al (2007) Rer1p competes with APH-1 for binding to nicastrin and regulates \u03b3-secretase complex assembly in the early secretory pathway. J Cell Biol 176:629\u2013640. https:\/\/doi.org\/10.1083\/jcb.200609180","journal-title":"J Cell Biol"},{"key":"232_CR157","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1177\/1073858407299730","volume":"13","author":"GE Stutzmann","year":"2007","unstructured":"Stutzmann GE (2007) The pathogenesis of Alzheimers disease\u2014is it a lifelong \u201cCalciumopathy\u201d. Neurosci 13:546\u2013559. https:\/\/doi.org\/10.1177\/1073858407299730","journal-title":"Neurosci"},{"key":"232_CR158","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1523\/JNEUROSCI.4386-03.2004","volume":"24","author":"GE Stutzmann","year":"2004","unstructured":"Stutzmann GE, Caccamo A, LaFerla FM, Parker I (2004) Dysregulated IP3 signaling in cortical neurons of Knock-in mice expressing an Alzheimer\u2019s-linked mutation in Presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. J Neurosci 24:508\u2013513. https:\/\/doi.org\/10.1523\/JNEUROSCI.4386-03.2004","journal-title":"J Neurosci"},{"key":"232_CR159","doi-asserted-by":"publisher","first-page":"E476","DOI":"10.1073\/pnas.1618657114","volume":"114","author":"L Sun","year":"2017","unstructured":"Sun L, Zhou R, Yang G, Shi Y (2017) Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of A\u03b242 and A\u03b240 peptides by \u03b3-secretase. Proc Natl Acad Sci 114:E476\u2013E485. https:\/\/doi.org\/10.1073\/pnas.1618657114","journal-title":"Proc Natl Acad Sci"},{"key":"232_CR160","doi-asserted-by":"publisher","first-page":"9637","DOI":"10.1073\/pnas.95.16.9637","volume":"95","author":"A Takashima","year":"1998","unstructured":"Takashima A, Murayama M, Murayama O et al (1998) Presenilin 1 associates with glycogen synthase kinase-3\u03b2 and its substrate tau. Proc Natl Acad Sci U S A 95:9637\u20139641. https:\/\/doi.org\/10.1073\/pnas.95.16.9637","journal-title":"Proc Natl Acad Sci U S A"},{"key":"232_CR161","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1001\/archneur.60.11.1541","volume":"60","author":"A Tedde","year":"2003","unstructured":"Tedde A, Nacmias B, Ciantelli M et al (2003) Identification of new Presenilin gene mutations in early-onset familial Alzheimer disease. Arch Neurol 60:1541\u20131544. https:\/\/doi.org\/10.1001\/archneur.60.11.1541","journal-title":"Arch Neurol"},{"key":"232_CR162","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3233\/JAD-2012-120280","volume":"31","author":"S Testi","year":"2012","unstructured":"Testi S, Fabrizi GM, Pompanin S, Cagnin A (2012) Autosomal dominant alzheimer\u2019s disease with early frontal lobe involvement associated with the Met239Ile mutation of presenilin 2 gene. J Alzheimers Dis 31:7\u201311. https:\/\/doi.org\/10.3233\/JAD-2012-120280","journal-title":"J Alzheimers Dis"},{"key":"232_CR163","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1093\/hmg\/9.3.325","volume":"9","author":"J Theuns","year":"2000","unstructured":"Theuns J, Del-Favero J, Dermaut B et al (2000) Genetic variability in the regulatory region of presenilin 1 associated with risk for Alzheimer\u2019s disease and variable expression. Hum Mol Genet 9:325\u2013331. https:\/\/doi.org\/10.1093\/hmg\/9.3.325","journal-title":"Hum Mol Genet"},{"key":"232_CR164","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1038\/nn1106-1354","volume":"9","author":"G Thinakaran","year":"2006","unstructured":"Thinakaran G, Sisodia SS (2006) Presenilins and Alzheimer disease: the calcium conspiracy. Nat Neurosci 9:1354\u20131355. https:\/\/doi.org\/10.1038\/nn1106-1354","journal-title":"Nat Neurosci"},{"key":"232_CR165","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/s0896-6273(00)80291-3","volume":"17","author":"G Thinakaran","year":"1996","unstructured":"Thinakaran G, Borchelt DR, Lee MK et al (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17:181\u2013190. https:\/\/doi.org\/10.1016\/s0896-6273(00)80291-3","journal-title":"Neuron"},{"key":"232_CR166","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1006\/NBDI.1998.0171","volume":"4","author":"G Thinakaran","year":"1998","unstructured":"Thinakaran G, Regard JB, Bouton CML et al (1998) Stable association of Presenilin derivatives and absence of Presenilin interactions with APP. Neurobiol Dis 4:438\u2013453. https:\/\/doi.org\/10.1006\/NBDI.1998.0171","journal-title":"Neurobiol Dis"},{"key":"232_CR167","doi-asserted-by":"publisher","first-page":"3557","DOI":"10.1038\/sj.onc.1209397","volume":"25","author":"MD To","year":"2006","unstructured":"To MD, Gokgoz N, Doyle TG et al (2006) Functional characterization of novel presenilin-2 variants identified in human breast cancers. Oncogene 25:3557\u20133564. https:\/\/doi.org\/10.1038\/sj.onc.1209397","journal-title":"Oncogene"},{"key":"232_CR168","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00415-006-0373-y","volume":"254","author":"C Tomaino","year":"2007","unstructured":"Tomaino C, Bernardi L, Anfossi M et al (2007) Presenilin 2 Ser130Leu mutation in a case of late-onset \u201csporadic\u201d Alzheimer\u2019s disease. J Neurol 254:391\u2013393","journal-title":"J Neurol"},{"key":"232_CR169","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1097\/WAD.0000000000000052","volume":"29","author":"L Tremolizzo","year":"2015","unstructured":"Tremolizzo L, Susani E, Mapelli C et al (2015) First report of PSEN2 mutation presenting as posterior cortical atrophy. Alzheimer Dis Assoc Disord 29:249\u2013251. https:\/\/doi.org\/10.1097\/WAD.0000000000000052","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"232_CR170","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.cell.2006.06.059","volume":"126","author":"H Tu","year":"2006","unstructured":"Tu H, Nelson O, Bezprozvanny A et al (2006) Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer\u2019s disease-linked mutations. Cell 126:981\u2013993. https:\/\/doi.org\/10.1016\/j.cell.2006.06.059","journal-title":"Cell"},{"key":"232_CR171","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jmb.2011.01.004","volume":"407","author":"S Turan","year":"2011","unstructured":"Turan S, Galla M, Ernst E et al (2011) Recombinase-mediated cassette exchange (RMCE): traditional concepts and current challenges. J Mol Biol 407:193\u2013221. https:\/\/doi.org\/10.1016\/j.jmb.2011.01.004","journal-title":"J Mol Biol"},{"key":"232_CR172","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3389\/fcell.2019.00197","volume":"7","author":"MS Uddin","year":"2019","unstructured":"Uddin MS, Kabir MT (2019) Emerging signal regulating potential of Genistein against Alzheimer\u2019s disease: a promising molecule of interest. Front Cell Dev Biol 7:197. https:\/\/doi.org\/10.3389\/fcell.2019.00197","journal-title":"Front Cell Dev Biol"},{"key":"232_CR173","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1159\/000481812","volume":"25","author":"MS Uddin","year":"2018","unstructured":"Uddin MS, Al Mamun A, Asaduzzaman M et al (2018a) Spectrum of disease and prescription pattern for outpatients with neurological disorders: an empirical pilot study in Bangladesh. Ann Neurosci 25:25\u201337. https:\/\/doi.org\/10.1159\/000481812","journal-title":"Ann Neurosci"},{"issue":"2","key":"232_CR174","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/psyg.12368","volume":"19","author":"MS Uddin","year":"2018","unstructured":"Uddin MS, Al Mamun A, Takeda S et al (2018b) Analyzing the chance of developing dementia among geriatric people: a cross-sectional pilot study in Bangladesh. Psychogeriatrics 19(2):87\u201394. https:\/\/doi.org\/10.1111\/psyg.12368","journal-title":"Psychogeriatrics"},{"key":"232_CR175","doi-asserted-by":"publisher","first-page":"101046","DOI":"10.1016\/J.ARR.2020.101046","volume":"60","author":"MS Uddin","year":"2020","unstructured":"Uddin MS, Devesh T, Al Mamun A et al (2020a) Circadian and sleep dysfunction in Alzheimer\u2019s disease. Ageing Res Rev 60:101046. https:\/\/doi.org\/10.1016\/J.ARR.2020.101046","journal-title":"Ageing Res Rev"},{"key":"232_CR176","doi-asserted-by":"publisher","first-page":"138313","DOI":"10.1016\/j.scitotenv.2020.138313","volume":"725","author":"MS Uddin","year":"2020","unstructured":"Uddin MS, Hossain MF, Al Mamun A et al (2020b) Exploring the multimodal role of phytochemicals in the modulation of cellular signaling pathways to combat age-related neurodegeneration. Sci Total Environ 725:138313. https:\/\/doi.org\/10.1016\/j.scitotenv.2020.138313","journal-title":"Sci Total Environ"},{"key":"232_CR177","doi-asserted-by":"publisher","first-page":"7039138","DOI":"10.1155\/2020\/7039138","volume":"2020","author":"MS Uddin","year":"2020","unstructured":"Uddin MS, Kabir MT, Jeandet P et al (2020c) Novel anti-Alzheimer\u2019s therapeutic molecules targeting amyloid precursor protein processing. Oxidative Med Cell Longev 2020:7039138. https:\/\/doi.org\/10.1155\/2020\/7039138","journal-title":"Oxidative Med Cell Longev"},{"key":"232_CR178","doi-asserted-by":"publisher","first-page":"106479","DOI":"10.1016\/j.intimp.2020.106479","volume":"84","author":"MS Uddin","year":"2020","unstructured":"Uddin MS, Kabir MT, Al Mamun A et al (2020d) Pharmacological approaches to mitigate neuroinflammation in Alzheimer\u2019s disease. Int Immunopharmacol 84:106479. https:\/\/doi.org\/10.1016\/j.intimp.2020.106479","journal-title":"Int Immunopharmacol"},{"key":"232_CR179","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.3390\/MOLECULES25061267","volume":"25","author":"MS Uddin","year":"2020","unstructured":"Uddin MS, Kabir MT, Niaz K et al (2020e) Molecular insight into the therapeutic promise of flavonoids against Alzheimer\u2019s disease. Mol 25:1267. https:\/\/doi.org\/10.3390\/MOLECULES25061267","journal-title":"Mol"},{"key":"232_CR180","doi-asserted-by":"publisher","unstructured":"Uddin MS, Kabir MT, Rahman MH et al (2020f) Exploring the multifunctional neuroprotective promise of rasagiline derivatives for multi-dysfunctional Alzheimer\u2019s disease. Curr Pharm Des 26. https:\/\/doi.org\/10.2174\/1381612826666200406075044","DOI":"10.2174\/1381612826666200406075044"},{"key":"232_CR181","doi-asserted-by":"publisher","unstructured":"Uddin MS, Kabir MT, Rahman MM, et al (2020g) TV 3326 for Alzheimer\u2019s dementia: a novel multimodal ChE and MAO inhibitors to mitigate Alzheimer\u2019s-like neuropathology. J Pharm Pharmacol 13244. https:\/\/doi.org\/10.1111\/jphp.13244","DOI":"10.1111\/jphp.13244"},{"key":"232_CR182","doi-asserted-by":"publisher","first-page":"134836","DOI":"10.1016\/j.scitotenv.2019.134836","volume":"700","author":"MS Uddin","year":"2020","unstructured":"Uddin MS, Kabir MT, Tewari D et al (2020h) Emerging signal regulating potential of small molecule biflavonoids to combat neuropathological insults of Alzheimer\u2019s disease. Sci Total Environ 700:134836","journal-title":"Sci Total Environ"},{"issue":"6","key":"232_CR183","doi-asserted-by":"publisher","first-page":"2654","DOI":"10.1007\/s12035-020-01911-8","volume":"57","author":"MS Uddin","year":"2020","unstructured":"Uddin MS, Rhman MM, Jakaria M, Rahman MS (2020i) Estrogen signaling in Alzheimer\u2019s disease: molecular insights and therapeutic targets for Alzheimer\u2019s dementia. Mol Neurobiol 57(6):2654\u20132670. https:\/\/doi.org\/10.1007\/s12035-020-01911-8","journal-title":"Mol Neurobiol"},{"key":"232_CR184","doi-asserted-by":"publisher","unstructured":"Uddin MS, Tewari D, Sharma G, et al (2020j) Molecular mechanisms of ER stress and UPR in the pathogenesis of Alzheimer\u2019s disease. Mol Neurobiol. https:\/\/doi.org\/10.1007\/s12035-020-01929-y","DOI":"10.1007\/s12035-020-01929-y"},{"key":"232_CR185","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1038\/mp.2015.177","volume":"21","author":"JI V\u00e9lez","year":"2016","unstructured":"V\u00e9lez JI, Lopera F, Sepulveda-Falla D et al (2016) APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer\u2019s disease. Mol Psychiatry 21:916\u2013924. https:\/\/doi.org\/10.1038\/mp.2015.177","journal-title":"Mol Psychiatry"},{"key":"232_CR186","doi-asserted-by":"publisher","first-page":"31025","DOI":"10.1074\/jbc.271.49.31025","volume":"271","author":"P Vito","year":"1996","unstructured":"Vito P, Wolozin B, Ganjei JK et al (1996) Requirement of the familial Alzheimer\u2019s disease gene PS2 for apoptosis. Opposing effect of ALG-3. J Biol Chem 271:31025\u201331028. https:\/\/doi.org\/10.1074\/jbc.271.49.31025","journal-title":"J Biol Chem"},{"key":"232_CR187","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1111\/j.1471-4159.2004.02858.x","volume":"92","author":"ES Walker","year":"2005","unstructured":"Walker ES, Martinez M, Brunkan AL, Goate A (2005a) Presenilin 2 familial Alzheimer\u2019s disease mutations result in partial loss of function and dramatic changes in A\u03b2 42\/40 ratios. J Neurochem 92:294\u2013301. https:\/\/doi.org\/10.1111\/j.1471-4159.2004.02858.x","journal-title":"J Neurochem"},{"key":"232_CR188","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1111\/j.1471-4159.2004.02858.x","volume":"92","author":"ES Walker","year":"2005","unstructured":"Walker ES, Martinez M, Brunkan AL, Goate A (2005b) Presenilin 2 familial Alzheimer\u2019s disease mutations result in partial loss of function and dramatic changes in Abeta 42\/40 ratios. J Neurochem 92:294\u2013301. https:\/\/doi.org\/10.1111\/j.1471-4159.2004.02858.x","journal-title":"J Neurochem"},{"key":"232_CR189","doi-asserted-by":"publisher","first-page":"847","DOI":"10.3233\/JAD-2012-120172","volume":"30","author":"D Wallon","year":"2012","unstructured":"Wallon D, Rousseau S, Rovelet-Lecrux A et al (2012) The french series of autosomal dominant early onset alzheimer\u2019s disease cases: mutation spectrum and cerebrospinal fluid biomarkers. J Alzheimers Dis 30:847\u2013856. https:\/\/doi.org\/10.3233\/JAD-2012-120172","journal-title":"J Alzheimers Dis"},{"key":"232_CR190","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1126\/science.1196284","volume":"330","author":"B Wang","year":"2010","unstructured":"Wang B, Yang W, Wen W et al (2010) \u03b3-Secretase gene mutations in familial acne inversa. Science 330:1065","journal-title":"Science"},{"key":"232_CR191","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1006\/neur.1996.0040","volume":"5","author":"RV Ward","year":"1996","unstructured":"Ward RV, Davis JB, Gray CW et al (1996) Presenilin\u20131 is processed into two major cleavage products in neuronal cell lines. Neurodegeneration 5:293\u2013298. https:\/\/doi.org\/10.1006\/neur.1996.0040","journal-title":"Neurodegeneration"},{"key":"232_CR192","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1038\/nm0995-848a","volume":"1","author":"W Wasco","year":"1995","unstructured":"Wasco W, Pettingell WP, Jondro PD et al (1995) Familial Alzheimer\u2019s chromosome 14 mutations. Nat Med 1:848\u2013848. https:\/\/doi.org\/10.1038\/nm0995-848a","journal-title":"Nat Med"},{"key":"232_CR193","doi-asserted-by":"publisher","first-page":"41967","DOI":"10.1074\/jbc.M509066200","volume":"280","author":"N Watanabe","year":"2005","unstructured":"Watanabe N, Tomita T, Sato C et al (2005) Pen-2 is incorporated into the \u03b3-secretase complex through binding to transmembrane domain 4 of Presenilin 1. J Biol Chem 280:41967\u201341975. https:\/\/doi.org\/10.1074\/jbc.M509066200","journal-title":"J Biol Chem"},{"key":"232_CR194","doi-asserted-by":"publisher","first-page":"5085","DOI":"10.1523\/JNEUROSCI.0317-12.2012","volume":"32","author":"H Watanabe","year":"2012","unstructured":"Watanabe H, Xia D, Kanekiyo T et al (2012) Familial frontotemporal dementia-associated Presenilin-1 c.548G>T mutation causes decreased mRNA expression and reduced presenilin function in knock-in mice. J Neurosci 32:5085\u20135096. https:\/\/doi.org\/10.1523\/JNEUROSCI.0317-12.2012","journal-title":"J Neurosci"},{"key":"232_CR195","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/alzrt107","volume":"4","author":"S Weggen","year":"2012","unstructured":"Weggen S, Beher D (2012) Molecular consequences of amyloid precursor protein and presenilin mutations causing autosomal-dominant Alzheimer\u2019s disease. Alzheimers Res Ther 4:1\u201314","journal-title":"Alzheimers Res Ther"},{"key":"232_CR196","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1097\/00005072-199809000-00004","volume":"57","author":"J Wegiel","year":"1998","unstructured":"Wegiel J, Wisniewski HM, Kuchna I et al (1998) Cell-type-specific enhancement of amyloid-\u03b2 deposition in a novel Presenilin-1 mutation (P117L). J Neuropathol Exp Neurol 57:831\u2013838. https:\/\/doi.org\/10.1097\/00005072-199809000-00004","journal-title":"J Neuropathol Exp Neurol"},{"key":"232_CR197","doi-asserted-by":"publisher","first-page":"e10195","DOI":"10.1371\/journal.pone.0010195","volume":"5","author":"M Wines-Samuelson","year":"2010","unstructured":"Wines-Samuelson M, Schulte EC, Smith MJ et al (2010) Characterization of age-dependent and progressive cortical neuronal degeneration in Presenilin conditional mutant mice. PLoS One 5:e10195. https:\/\/doi.org\/10.1371\/journal.pone.0010195","journal-title":"PLoS One"},{"key":"232_CR198","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1001\/archneurol.2011.221","volume":"69","author":"TS Wingo","year":"2012","unstructured":"Wingo TS, Lah JJ, Levey AI, Cutler DJ (2012) Autosomal recessive causes likely in early-onset Alzheimer disease. Arch Neurol 69:59\u201364. https:\/\/doi.org\/10.1001\/archneurol.2011.221","journal-title":"Arch Neurol"},{"key":"232_CR199","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/sj.embor.7400896","volume":"8","author":"MS Wolfe","year":"2007","unstructured":"Wolfe MS (2007) When loss is gain: reduced presenilin proteolytic function leads to increased A\u03b242\/A\u03b240. Talking point on the role of presenilin mutations in Alzheimer disease. EMBO Rep 8:136\u2013140. https:\/\/doi.org\/10.1038\/sj.embor.7400896","journal-title":"EMBO Rep"},{"key":"232_CR200","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/19077","volume":"398","author":"MS Wolfe","year":"1999","unstructured":"Wolfe MS, Xia W, Ostaszewski BL et al (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and \u03b3-secretase activity. Nature 398:513\u2013517. https:\/\/doi.org\/10.1038\/19077","journal-title":"Nature"},{"key":"232_CR201","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.neuron.2015.02.010","volume":"85","author":"D Xia","year":"2015","unstructured":"Xia D, Watanabe H, Wu B et al (2015) Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer\u2019s disease. Neuron 85:967\u2013981. https:\/\/doi.org\/10.1016\/j.neuron.2015.02.010","journal-title":"Neuron"},{"key":"232_CR202","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.neuron.2016.03.009","volume":"90","author":"D Xia","year":"2016","unstructured":"Xia D, Kelleher RJ, Shen J (2016) Loss of A\u03b243 production caused by Presenilin-1 mutations in the knockin mouse brain. Neuron 90:417\u2013422. https:\/\/doi.org\/10.1016\/j.neuron.2016.03.009","journal-title":"Neuron"},{"key":"232_CR203","doi-asserted-by":"publisher","first-page":"28135","DOI":"10.1074\/jbc.M110871200","volume":"277","author":"D-S Yang","year":"2002","unstructured":"Yang D-S, Tandon A, Chen F et al (2002) Mature glycosylation and trafficking of nicastrin modulate its binding to presenilins. J Biol Chem 277:28135\u201328142. https:\/\/doi.org\/10.1074\/jbc.M110871200","journal-title":"J Biol Chem"},{"key":"232_CR204","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1001\/archneur.56.1.65","volume":"56","author":"M Yasuda","year":"1999","unstructured":"Yasuda M, Maeda K, Hashimoto M et al (1999) A pedigree with a novel Presenilin 1 mutation at a residue that is not conserved in Presenilin 2. Arch Neurol 56:65. https:\/\/doi.org\/10.1001\/archneur.56.1.65","journal-title":"Arch Neurol"},{"key":"232_CR205","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/1471-2377-14-105","volume":"14","author":"YC Youn","year":"2014","unstructured":"Youn YC, Bagyinszky E, Kim H et al (2014a) Probable novel PSEN2 Val214Leu mutation in Alzheimer\u2019s disease supported by structural prediction. BMC Neurol 14:105. https:\/\/doi.org\/10.1186\/1471-2377-14-105","journal-title":"BMC Neurol"},{"key":"232_CR206","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/1471-2377-14-105","volume":"14","author":"YC Youn","year":"2014","unstructured":"Youn YC, Bagyinszky E, Kim HR et al (2014b) Probable novel PSEN2 Val214Leu mutation in Alzheimer\u2019s disease supported by structural prediction. BMC Neurol 14:105. https:\/\/doi.org\/10.1186\/1471-2377-14-105","journal-title":"BMC Neurol"},{"key":"232_CR207","doi-asserted-by":"publisher","first-page":"16470","DOI":"10.1074\/jbc.273.26.16470","volume":"273","author":"G Yu","year":"1998","unstructured":"Yu G, Chen F, Levesque G et al (1998) The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin. J Biol Chem 273:16470\u201316475. https:\/\/doi.org\/10.1074\/jbc.273.26.16470","journal-title":"J Biol Chem"},{"key":"232_CR208","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/35024009","volume":"407","author":"G Yu","year":"2000","unstructured":"Yu G, Nishimura M, Arawaka S et al (2000) Nicastrin modulates presenilin-mediated notch\/glp-1 signal transduction and \u03b2APP processing. Nature 407:48\u201354. https:\/\/doi.org\/10.1038\/35024009","journal-title":"Nature"},{"key":"232_CR209","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.nbd.2003.11.002","volume":"15","author":"G Zatti","year":"2004","unstructured":"Zatti G, Ghidoni R, Barbiero L et al (2004) The presenilin 2 M239I mutation associated with familial Alzheimer\u2019s disease reduces Ca2+ release from intracellular stores. Neurobiol Dis 15:269\u2013278. https:\/\/doi.org\/10.1016\/j.nbd.2003.11.002","journal-title":"Neurobiol Dis"},{"key":"232_CR210","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.ceca.2006.03.002","volume":"39","author":"G Zatti","year":"2006","unstructured":"Zatti G, Burgo A, Giacomello M et al (2006) Presenilin mutations linked to familial Alzheimer\u2019s disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium 39:539\u2013550. https:\/\/doi.org\/10.1016\/j.ceca.2006.03.002","journal-title":"Cell Calcium"},{"key":"232_CR211","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/27208","volume":"395","author":"Z Zhang","year":"1998","unstructured":"Zhang Z, Hartmann H, Minh Do V et al (1998) Destabilization of \u03b2-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. Nature 395:698\u2013702. https:\/\/doi.org\/10.1038\/27208","journal-title":"Nature"},{"key":"232_CR212","doi-asserted-by":"publisher","first-page":"17020","DOI":"10.1074\/jbc.M409467200","volume":"280","author":"Y Zhang","year":"2005","unstructured":"Zhang Y, Luo W, Wang H et al (2005) Nicastrin is critical for stability and trafficking but not association of other presenilin\/\u03b3-secretase components. J Biol Chem 280:17020\u201317026. https:\/\/doi.org\/10.1074\/jbc.M409467200","journal-title":"J Biol Chem"},{"key":"232_CR213","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/nature08177","volume":"460","author":"C Zhang","year":"2009","unstructured":"Zhang C, Wu B, Beglopoulos V et al (2009) Presenilins are essential for regulating neurotransmitter release. Nature 460:632\u2013636. https:\/\/doi.org\/10.1038\/nature08177","journal-title":"Nature"},{"key":"232_CR214","doi-asserted-by":"publisher","first-page":"20356","DOI":"10.1074\/jbc.M112.349738","volume":"287","author":"J Zheng","year":"2012","unstructured":"Zheng J, Watanabe H, Wines-Samuelson M et al (2012) Conditional deletion of Notch1 and Notch2 genes in excitatory neurons of postnatal forebrain does not cause neurodegeneration or reduction of Notch mRNAs and proteins. J Biol Chem 287:20356\u201320368. https:\/\/doi.org\/10.1074\/jbc.M112.349738","journal-title":"J Biol Chem"}],"container-title":["Neurotoxicity Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-020-00232-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12640-020-00232-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-020-00232-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T23:21:58Z","timestamp":1623972118000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12640-020-00232-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,18]]},"references-count":214,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["232"],"URL":"https:\/\/doi.org\/10.1007\/s12640-020-00232-x","relation":{},"ISSN":["1029-8428","1476-3524"],"issn-type":[{"value":"1029-8428","type":"print"},{"value":"1476-3524","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,18]]},"assertion":[{"value":"18 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}