{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:01:57Z","timestamp":1790960517773,"version":"4.1.0"},"reference-count":109,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer\u2019s disease (AD) is characterized by progressive synaptic dysfunction, neuronal death, and brain atrophy, with amyloid-\u03b2 (A\u03b2) plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue, which all lead to loss of cognitive function. Pathogenic mutations in the well-known AD causal genes including <jats:italic>APP<\/jats:italic>, <jats:italic>PSEN1<\/jats:italic>, and <jats:italic>PSEN2<\/jats:italic> impair a variety of pathways, including protein processing, axonal transport, and metabolic homeostasis. Here we identified a missense variant rs117916664 (c.896T&gt;C, p.Asn299Ser [p.N299S]) of the acetyl-CoA acyltransferase 1 (<jats:italic>ACAA1<\/jats:italic>) gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort. Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity, impairing lysosomal function, and aggravating the A\u03b2 pathology and neuronal loss, which finally caused cognitive impairment in a murine model. Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.<\/jats:p>","DOI":"10.1038\/s41392-021-00748-4","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T09:03:59Z","timestamp":1630400639000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["A novel missense variant in ACAA1 contributes to early-onset Alzheimer\u2019s disease, impairs lysosomal function, and facilitates amyloid-\u03b2 pathology and cognitive decline"],"prefix":"10.1038","volume":"6","author":[{"given":"Rongcan","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maosen","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deng-Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Xiu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nengyin","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2955-0693","authenticated-orcid":false,"given":"Yong-Gang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"748_CR1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1056\/NEJMra0909142","volume":"362","author":"HW Querfurth","year":"2010","unstructured":"Querfurth, H. W. & LaFerla, F. M. Alzheimer\u2019s disease. N. Engl. J. Med. 362, 329\u2013344 (2010).","journal-title":"N. Engl. J. Med."},{"key":"748_CR2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","volume":"7","author":"DS Knopman","year":"2021","unstructured":"Knopman, D. S. et al. Alzheimer disease. Nat. Rev. Dis. Prim. 7, 33 (2021).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"748_CR3","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1001\/archpsyc.63.2.168","volume":"63","author":"M Gatz","year":"2006","unstructured":"Gatz, M. et al. Role of genes and environments for explaining Alzheimer disease. Arch. Gen. Psychiatry 63, 168\u2013174 (2006).","journal-title":"Arch. Gen. Psychiatry"},{"key":"748_CR4","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/ana.10999","volume":"55","author":"NL Pedersen","year":"2004","unstructured":"Pedersen, N. L., Gatz, M., Berg, S. & Johansson, B. How heritable is Alzheimer\u2019s disease late in life? Findings from Swedish twins. Ann. Neurol. 55, 180\u2013185 (2004).","journal-title":"Ann. Neurol."},{"key":"748_CR5","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.cell.2013.10.037","volume":"155","author":"R Guerreiro","year":"2013","unstructured":"Guerreiro, R., Bras, J. & Hardy, J. SnapShot: genetics of Alzheimer\u2019s disease. Cell 155, 968 (2013).","journal-title":"Cell"},{"key":"748_CR6","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1126\/science.2880399","volume":"235","author":"PH Stgeorgehyslop","year":"1987","unstructured":"Stgeorgehyslop, P. H. et al. The genetic-defect causing familial Alzheimers disease maps on chromosome-21. Science 235, 885\u2013890 (1987).","journal-title":"Science"},{"key":"748_CR7","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1126\/science.2949367","volume":"235","author":"RE Tanzi","year":"1987","unstructured":"Tanzi, R. E. et al. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235, 880\u2013884 (1987).","journal-title":"Science"},{"key":"748_CR8","first-page":"563","volume":"48","author":"GD Schellenberg","year":"1991","unstructured":"Schellenberg, G. D. et al. Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. Am. J. Hum. Genet. 48, 563\u2013583 (1991).","journal-title":"Am. J. Hum. Genet."},{"key":"748_CR9","first-page":"998","volume":"51","author":"K Kamino","year":"1992","unstructured":"Kamino, K. et al. Linkage and mutational analysis of familial Alzheimer-disease kindreds for the App gene region. Am. J. Hum. Genet. 51, 998\u20131014 (1992).","journal-title":"Am. J. Hum. Genet."},{"key":"748_CR10","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1126\/science.1411576","volume":"258","author":"GD Schellenberg","year":"1992","unstructured":"Schellenberg, G. D. et al. Genetic-linkage evidence for a familial Alzheimers-disease locus on chromosome-14. Science 258, 668\u2013671 (1992).","journal-title":"Science"},{"key":"748_CR11","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/ng1292-330","volume":"2","author":"P Stgeorgehyslop","year":"1992","unstructured":"Stgeorgehyslop, P. et al. Genetic-evidence for a novel familial Alzheimers disease locus on chromosome-14. Nat. Genet. 2, 330\u2013334 (1992).","journal-title":"Nat. Genet."},{"key":"748_CR12","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1086\/302553","volume":"65","author":"D Campion","year":"1999","unstructured":"Campion, D. et al. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am. J. Hum. Genet. 65, 664\u2013670 (1999).","journal-title":"Am. J. Hum. Genet."},{"key":"748_CR13","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1021\/acschemneuro.8b00435","volume":"10","author":"DF Zhang","year":"2019","unstructured":"Zhang, D. F., Xu, M., Bi, R. & Yao, Y. G. Genetic analyses of Alzheimer\u2019s disease in China: achievements and perspectives. ACS Chem. Neurosci. 10, 890\u2013901 (2019).","journal-title":"ACS Chem. Neurosci."},{"key":"748_CR14","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/S1474-4422(19)30435-1","volume":"19","author":"SJ Andrews","year":"2020","unstructured":"Andrews, S. J., Fulton-Howard, B. & Goate, A. Interpretation of risk loci from genome-wide association studies of Alzheimer\u2019s disease. Lancet Neurol. 19, 326\u2013335 (2020).","journal-title":"Lancet Neurol."},{"key":"748_CR15","doi-asserted-by":"publisher","first-page":"200.e13","DOI":"10.1016\/j.neurobiolaging.2016.02.024","volume":"41","author":"PG Ridge","year":"2016","unstructured":"Ridge, P. G. et al. Assessment of the genetic variance of late-onset Alzheimer\u2019s disease. Neurobiol. Aging 41, 200.e13\u2013200.e20 (2016).","journal-title":"Neurobiol. Aging"},{"key":"748_CR16","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/ng.2802","volume":"45","author":"JC Lambert","year":"2013","unstructured":"Lambert, J. C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer\u2019s disease. Nat. Genet. 45, 1452\u20131458 (2013).","journal-title":"Nat. Genet."},{"key":"748_CR17","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/s41588-020-00776-w","volume":"53","author":"J Schwartzentruber","year":"2021","unstructured":"Schwartzentruber, J. et al. Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer\u2019s disease risk genes. Nat. Genet. 53, 392\u2013402 (2021).","journal-title":"Nat. Genet."},{"key":"748_CR18","doi-asserted-by":"publisher","first-page":"e79771","DOI":"10.1371\/journal.pone.0079771","volume":"8","author":"PGEA Ridge","year":"2013","unstructured":"Ridge, P. G. E. A. Alzheimer\u2019s disease: analyzing the missing heritability. PLoS ONE 8, e79771 (2013).","journal-title":"PLoS ONE"},{"key":"748_CR19","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1038\/s41588-020-0696-0","volume":"52","author":"R Nativio","year":"2020","unstructured":"Nativio, R. et al. An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer\u2019s disease. Nat. Genet. 52, 1024\u20131035 (2020).","journal-title":"Nat. Genet."},{"key":"748_CR20","doi-asserted-by":"publisher","first-page":"538301","DOI":"10.3389\/fneur.2020.538301","volume":"11","author":"X Xiao","year":"2020","unstructured":"Xiao, X., Liu, X. & Jiao, B. Epigenetics: recent advances and its role in the treatment of Alzheimer\u2019s disease. Front. Neurol. 11, 538301 (2020).","journal-title":"Front. Neurol."},{"key":"748_CR21","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1093\/nsr\/nwy127","volume":"6","author":"DF Zhang","year":"2019","unstructured":"Zhang, D. F. et al. Complement C7 is a novel risk gene for Alzheimer\u2019s disease in Han Chinese. Natl Sci. Rev. 6, 257\u2013274 (2019).","journal-title":"Natl Sci. Rev."},{"key":"748_CR22","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.biopsych.2014.05.006","volume":"77","author":"CM Karch","year":"2015","unstructured":"Karch, C. M. & Goate, A. M. Alzheimer\u2019s disease risk genes and mechanisms of disease pathogenesis. Biol. Psychiatry 77, 43\u201351 (2015).","journal-title":"Biol. Psychiatry"},{"key":"748_CR23","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-3-319-72938-1_3","volume":"2018","author":"M Ghani","year":"2018","unstructured":"Ghani, M., Reitz, C., George-Hyslop, P. & Rogaeva, E. Genetic complexity of early-onset Alzheimer\u2019s disease. Neurodegener. Dis. 2018, 29\u201350 (2018).","journal-title":"Neurodegener. Dis."},{"key":"748_CR24","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/nrneurol.2017.111","volume":"13","author":"J Wang","year":"2017","unstructured":"Wang, J., Gu, B. J., Masters, C. L. & Wang, Y. J. A systemic view of Alzheimer disease - insights from amyloid-beta metabolism beyond the brain. Nat. Rev. Neurol. 13, 612\u2013623 (2017).","journal-title":"Nat. Rev. Neurol."},{"key":"748_CR25","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41583-019-0132-6","volume":"20","author":"DA Butterfield","year":"2019","unstructured":"Butterfield, D. A. & Halliwell, B. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat. Rev. Neurosci. 20, 148\u2013160 (2019).","journal-title":"Nat. Rev. Neurosci."},{"key":"748_CR26","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41591-020-0815-6","volume":"26","author":"ECB Johnson","year":"2020","unstructured":"Johnson, E. C. B. et al. Large-scale proteomic analysis of Alzheimer\u2019s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat. Med. 26, 769\u2013780 (2020).","journal-title":"Nat. Med."},{"key":"748_CR27","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.jalz.2017.01.020","volume":"13","author":"JB Toledo","year":"2017","unstructured":"Toledo, J. B. et al. Metabolic network failures in Alzheimer\u2019s disease: a biochemical road map. Alzheimers Dement. 13, 965\u2013984 (2017).","journal-title":"Alzheimers Dement."},{"key":"748_CR28","doi-asserted-by":"crossref","unstructured":"Mahajan, U. V. et al. Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: a targeted metabolomic and transcriptomic study. PLoS Med. 17, e1003012 (2020).","DOI":"10.1371\/journal.pmed.1003012"},{"key":"748_CR29","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nature15394","volume":"526","author":"PH Sudmant","year":"2015","unstructured":"Sudmant, P. H. et al. An integrated map of structural variation in 2,504 human genomes. Nature 526, 75\u201381 (2015).","journal-title":"Nature"},{"key":"748_CR30","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jpsychires.2019.03.026","volume":"113","author":"G Wang","year":"2019","unstructured":"Wang, G. et al. Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer\u2019s disease. J. Psychiatr. Res. 113, 141\u2013147 (2019).","journal-title":"J. Psychiatr. Res."},{"key":"748_CR31","doi-asserted-by":"publisher","first-page":"D886","DOI":"10.1093\/nar\/gky1016","volume":"47","author":"P Rentzsch","year":"2019","unstructured":"Rentzsch, P., Witten, D., Cooper, G. M., Shendure, J. & Kircher, M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 47, D886\u2013D894 (2019).","journal-title":"Nucleic Acids Res."},{"key":"748_CR32","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"The 1000 Genomes Project Consortium.","year":"2015","unstructured":"The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 526, 68\u201374 (2015).","journal-title":"Nature"},{"key":"748_CR33","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature19057","volume":"536","author":"M Lek","year":"2016","unstructured":"Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285\u2013291 (2016).","journal-title":"Nature"},{"key":"748_CR34","doi-asserted-by":"publisher","first-page":"e1003286","DOI":"10.1371\/journal.pgen.1003286","volume":"9","author":"Y Mizuno","year":"2013","unstructured":"Mizuno, Y. et al. Tysnd1 deficiency in mice interferes with the peroxisomal localization of PTS2 enzymes, causing lipid metabolic abnormalities and male infertility. PLoS Genet. 9, e1003286 (2013).","journal-title":"PLoS Genet."},{"key":"748_CR35","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1021\/acschembio.6b01001","volume":"12","author":"JL Counihan","year":"2017","unstructured":"Counihan, J. L. et al. Chemoproteomic profiling of acetanilide herbicides reveals their role in inhibiting fatty acid oxidation. ACS Chem. Biol. 12, 635\u2013642 (2017).","journal-title":"ACS Chem. Biol."},{"key":"748_CR36","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1038\/npp.2015.232","volume":"41","author":"DF Zhang","year":"2016","unstructured":"Zhang, D. F. et al. CFH variants affect structural and functional brain changes and genetic risk of Alzheimer\u2019s disease. Neuropsychopharmacology 41, 1034\u20131045 (2016).","journal-title":"Neuropsychopharmacology"},{"key":"748_CR37","doi-asserted-by":"publisher","first-page":"5192","DOI":"10.1007\/s12035-016-0065-2","volume":"54","author":"Q Xiang","year":"2017","unstructured":"Xiang, Q. et al. Rare genetic variants of the Transthyretin gene are associated with Alzheimer\u2019s disease in Han Chinese. Mol. Neurobiol. 54, 5192\u20135200 (2017).","journal-title":"Mol. Neurobiol."},{"key":"748_CR38","doi-asserted-by":"publisher","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","volume":"45","author":"M Kanehisa","year":"2017","unstructured":"Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y. & Morishima, K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 45, D353\u2013D361 (2017).","journal-title":"Nucleic Acids Res."},{"key":"748_CR39","doi-asserted-by":"publisher","first-page":"D330","DOI":"10.1093\/nar\/gky1055","volume":"47","author":"The Gene Ontology Consortium.","year":"2019","unstructured":"The Gene Ontology Consortium. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res. 47, D330\u2013D338 (2019).","journal-title":"Nucleic Acids Res."},{"key":"748_CR40","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"748_CR41","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jalz.2017.08.012","volume":"14","author":"M Xu","year":"2018","unstructured":"Xu, M. et al. A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer\u2019s disease. Alzheimers Dement. 14, 215\u2013229 (2018).","journal-title":"Alzheimers Dement."},{"key":"748_CR42","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","volume":"278","author":"LA Farrer","year":"1997","unstructured":"Farrer, L. A. et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease - a meta-analysis. JAMA 278, 1349\u20131356 (1997).","journal-title":"JAMA"},{"key":"748_CR43","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/mp.2011.52","volume":"16","author":"E Genin","year":"2011","unstructured":"Genin, E. et al. APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol. Psychiatry 16, 903\u2013907 (2011).","journal-title":"Mol. Psychiatry"},{"key":"748_CR44","doi-asserted-by":"crossref","unstructured":"Bras, J. et al. Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer\u2019s disease identifies a homozygous CTSF mutation. Neurobiol. Aging 46, 236.e1\u2013236.e6 (2016).","DOI":"10.1016\/j.neurobiolaging.2016.06.018"},{"key":"748_CR45","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1038\/sj.mp.4001709","volume":"10","author":"RA Sweet","year":"2005","unstructured":"Sweet, R. A. et al. Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease. Mol. Psychiatry 10, 1026\u20131036 (2005).","journal-title":"Mol. Psychiatry"},{"key":"748_CR46","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/j.cell.2010.05.008","volume":"141","author":"JH Lee","year":"2010","unstructured":"Lee, J. H. et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141, 1146\u20131158 (2010).","journal-title":"Cell"},{"key":"748_CR47","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/hmg\/ddh019","volume":"13","author":"JL Jankowsky","year":"2004","unstructured":"Jankowsky, J. L. et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13, 159\u2013170 (2004).","journal-title":"Hum. Mol. Genet."},{"key":"748_CR48","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/ng1094-148","volume":"8","author":"MG Kaplitt","year":"1994","unstructured":"Kaplitt, M. G. et al. Long-term gene-expression and phenotypic correction using adenoassociated virus vectors in the mammalian brain. Nat. Genet. 8, 148\u2013154 (1994).","journal-title":"Nat. Genet."},{"key":"748_CR49","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/S1474-4422(10)70254-4","volume":"9","author":"WJ Marks Jr.","year":"2010","unstructured":"Marks, W. J. Jr. et al. Gene delivery of AAV2-neurturin for Parkinson\u2019s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 9, 1164\u20131172 (2010).","journal-title":"Lancet Neurol."},{"key":"748_CR50","doi-asserted-by":"crossref","first-page":"88","DOI":"10.24272\/j.issn.2095-8137.2017.015","volume":"38","author":"SH Wu","year":"2017","unstructured":"Wu, S. H. et al. Comparative study of the transfection efficiency of commonly used viral vectors in rhesus monkey (Macaca mulatta) brains. Zool. Res. 38, 88\u201395 (2017).","journal-title":"Zool. Res."},{"key":"748_CR51","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.1038\/s41380-019-0483-4","volume":"25","author":"S Hijazi","year":"2020","unstructured":"Hijazi, S. et al. Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer\u2019s disease. Mol. Psychiatry 25, 3380\u20133398 (2020).","journal-title":"Mol. Psychiatry"},{"key":"748_CR52","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s12264-011-1015-7","volume":"27","author":"H Xiong","year":"2011","unstructured":"Xiong, H. et al. Biochemical and behavioral characterization of the double transgenic mouse model (APPswe\/PS1dE9) of Alzheimer\u2019s disease. Neurosci. Bull. 27, 221\u2013232 (2011).","journal-title":"Neurosci. Bull."},{"key":"748_CR53","doi-asserted-by":"publisher","first-page":"E2705","DOI":"10.1073\/pnas.1604032113","volume":"113","author":"AKY Fu","year":"2016","unstructured":"Fu, A. K. Y. et al. IL-33 ameliorates Alzheimer\u2019s disease-like pathology and cognitive decline. Proc. Natl Acad. Sci. USA 113, E2705\u2013E2713 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"748_CR54","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1080\/15548627.2019.1596488","volume":"16","author":"R Luo","year":"2020","unstructured":"Luo, R. et al. Activation of PPARA-mediated autophagy reduces Alzheimer disease-like pathology and cognitive decline in a murine model. Autophagy 16, 52\u201369 (2020).","journal-title":"Autophagy"},{"key":"748_CR55","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1093\/brain\/awx109","volume":"140","author":"S Alves","year":"2017","unstructured":"Alves, S. et al. Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer\u2019s disease mice. Brain 140, 826\u2013842 (2017).","journal-title":"Brain"},{"key":"748_CR56","doi-asserted-by":"publisher","first-page":"a006338","DOI":"10.1101\/cshperspect.a006338","volume":"2","author":"L Mucke","year":"2012","unstructured":"Mucke, L. & Selkoe, D. J. Neurotoxicity of amyloid beta-protein: synaptic and network dysfunction. Cold Spring Harb. Perspect. Med. 2, a006338 (2012).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"748_CR57","doi-asserted-by":"publisher","first-page":"7817","DOI":"10.1523\/JNEUROSCI.6412-10.2011","volume":"31","author":"S Lee","year":"2011","unstructured":"Lee, S., Sato, Y. & Nixon, R. A. Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer\u2019s-like axonal dystrophy. J. Neurosci. 31, 7817\u20137830 (2011).","journal-title":"J. Neurosci."},{"key":"748_CR58","doi-asserted-by":"publisher","first-page":"6926","DOI":"10.1523\/JNEUROSCI.0800-08.2008","volume":"28","author":"B Boland","year":"2008","unstructured":"Boland, B. et al. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer\u2019s disease. J. Neurosci. 28, 6926\u20136937 (2008).","journal-title":"J. Neurosci."},{"key":"748_CR59","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.biopsych.2019.05.008","volume":"87","author":"A Di Meco","year":"2020","unstructured":"Di Meco, A., Curtis, M. E., Lauretti, E. & Pratico, D. Autophagy dysfunction in Alzheimer\u2019s disease: mechanistic insights and new therapeutic opportunities. Biol. Psychiatry 87, 797\u2013807 (2020).","journal-title":"Biol. Psychiatry"},{"key":"748_CR60","doi-asserted-by":"publisher","first-page":"585","DOI":"10.4161\/auto.5.5.8823","volume":"5","author":"DC Rubinsztein","year":"2009","unstructured":"Rubinsztein, D. C. et al. In search of an \u201cautophagomometer\u201d. Autophagy 5, 585\u2013589 (2009).","journal-title":"Autophagy"},{"key":"748_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","volume":"17","author":"DJ Klionsky","year":"2021","unstructured":"Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy 17, 1\u2013382 (2021).","journal-title":"Autophagy"},{"key":"748_CR62","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1073\/pnas.1619253114","volume":"114","author":"N Sheng","year":"2017","unstructured":"Sheng, N., Shi, Y. S. & Nicoll, R. A. Amino-terminal domains of kainate receptors determine the differential dependence on Neto auxiliary subunits for trafficking. Proc. Natl Acad. Sci. USA 114, 1159\u20131164 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"748_CR63","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/S0166-2236(02)02215-4","volume":"25","author":"BA Tsui-Pierchala","year":"2002","unstructured":"Tsui-Pierchala, B. A., Encinas, M., Milbrandt, J. & Johnson, E. M. Jr. Lipid rafts in neuronal signaling and function. Trends Neurosci. 25, 412\u2013417 (2002).","journal-title":"Trends Neurosci."},{"key":"748_CR64","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.devcel.2020.06.012","volume":"55","author":"X Wu","year":"2020","unstructured":"Wu, X., Cai, Q., Feng, Z. & Zhang, M. Liquid-liquid phase separation in neuronal development and synaptic signaling. Dev. Cell 55, 18\u201329 (2020).","journal-title":"Dev. Cell"},{"key":"748_CR65","doi-asserted-by":"publisher","first-page":"719.e6","DOI":"10.1016\/j.cmet.2017.08.024","volume":"26","author":"L Liu","year":"2017","unstructured":"Liu, L., MacKenzie, K. R., Putluri, N., Maletic-Savatic, M. & Bellen, H. J. The glia-neuron lactate lhuttle and elevated ROS promote lipid synthesis in neurons and lipid droplet accumulation in glia via APOE\/D. Cell Metab. 26, 719.e6\u2013737.e6 (2017).","journal-title":"Cell Metab."},{"key":"748_CR66","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.cell.2014.12.019","volume":"160","author":"L Liu","year":"2015","unstructured":"Liu, L. et al. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell 160, 177\u2013190 (2015).","journal-title":"Cell"},{"key":"748_CR67","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.bbalip.2010.01.001","volume":"1801","author":"RJ Wanders","year":"2010","unstructured":"Wanders, R. J., Ferdinandusse, S., Brites, P. & Kemp, S. Peroxisomes, lipid metabolism and lipotoxicity. Biochim. Biophys. Acta 1801, 272\u2013280 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"748_CR68","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1038\/s12276-020-00503-9","volume":"52","author":"DS Jo","year":"2020","unstructured":"Jo, D. S., Park, N. Y. & Cho, D. H. Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases. Exp. Mol. Med. 52, 1486\u20131495 (2020).","journal-title":"Exp. Mol. Med."},{"key":"748_CR69","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s00401-011-0836-9","volume":"122","author":"J Kou","year":"2011","unstructured":"Kou, J. et al. Peroxisomal alterations in Alzheimer\u2019s disease. Acta Neuropathol. 122, 271\u2013283 (2011).","journal-title":"Acta Neuropathol."},{"key":"748_CR70","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.tem.2016.12.003","volume":"28","author":"CM Cipolla","year":"2017","unstructured":"Cipolla, C. M. & Lodhi, I. J. Peroxisomal dysfunction in age-related diseases. Trends Endocrinol. Metab. 28, 297\u2013308 (2017).","journal-title":"Trends Endocrinol. Metab."},{"key":"748_CR71","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1242\/dmm.007419","volume":"4","author":"FD Mast","year":"2011","unstructured":"Mast, F. D. et al. A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders. Dis. Model. Mech. 4, 659\u2013672 (2011).","journal-title":"Dis. Model. Mech."},{"key":"748_CR72","doi-asserted-by":"crossref","unstructured":"Wangler, M. F. et al. Peroxisomal biogenesis is genetically and biochemically linked to carbohydrate metabolism in Drosophila and mouse. PLoS Genet. 13, e1006825 (2017).","DOI":"10.1371\/journal.pgen.1006825"},{"key":"748_CR73","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/ng2070","volume":"39","author":"CM Kassmann","year":"2007","unstructured":"Kassmann, C. M. et al. Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes. Nat. Genet. 39, 969\u2013976 (2007).","journal-title":"Nat. Genet."},{"key":"748_CR74","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1002\/glia.21027","volume":"58","author":"A Bottelbergs","year":"2010","unstructured":"Bottelbergs, A. et al. Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytes. Glia 58, 1532\u20131543 (2010).","journal-title":"Glia"},{"key":"748_CR75","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/ng0997-49","volume":"17","author":"M Baes","year":"1997","unstructured":"Baes, M. et al. A mouse model for Zellweger syndrome. Nat. Genet. 17, 49\u201357 (1997).","journal-title":"Nat. Genet."},{"key":"748_CR76","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.ydbio.2014.08.026","volume":"395","author":"MG Hanson","year":"2014","unstructured":"Hanson, M. G., Fregoso, V. L., Vrana, J. D., Tucker, C. L. & Niswander, L. A. Peripheral nervous system defects in a mouse model for peroxisomal biogenesis disorders. Dev. Biol. 395, 84\u201395 (2014).","journal-title":"Dev. Biol."},{"key":"748_CR77","doi-asserted-by":"publisher","first-page":"589.e6","DOI":"10.1016\/j.neuron.2020.02.021","volume":"106","author":"HL Chung","year":"2020","unstructured":"Chung, H. L. et al. Loss- or gain-of-function mutations in ACOX1 cause axonal loss via different mechanisms. Neuron 106, 589.e6\u2013606.e6 (2020).","journal-title":"Neuron"},{"key":"748_CR78","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1002\/glia.22831","volume":"63","author":"S Verheijden","year":"2015","unstructured":"Verheijden, S. et al. Identification of a chronic non-neurodegenerative microglia activation state in a mouse model of peroxisomal beta-oxidation deficiency. Glia 63, 1606\u20131620 (2015).","journal-title":"Glia"},{"key":"748_CR79","doi-asserted-by":"publisher","first-page":"5907","DOI":"10.1073\/pnas.0901229106","volume":"106","author":"G Pigino","year":"2009","unstructured":"Pigino, G. et al. Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. Proc. Natl Acad. Sci. USA 106, 5907\u20135912 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"748_CR80","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1126\/science.1105681","volume":"307","author":"GB Stokin","year":"2005","unstructured":"Stokin, G. B. et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer\u2019s disease. Science 307, 1282\u20131288 (2005).","journal-title":"Science"},{"key":"748_CR81","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1016\/j.bbamcr.2006.09.006","volume":"1763","author":"M Schrader","year":"2006","unstructured":"Schrader, M. & Fahimi, H. D. Peroxisomes and oxidative stress. Biochim. Biophys. Acta 1763, 1755\u20131766 (2006).","journal-title":"Biochim. Biophys. Acta"},{"key":"748_CR82","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1042\/bst0290250","volume":"29","author":"RJ Wanders","year":"2001","unstructured":"Wanders, R. J. et al. Peroxisomal fatty acid alpha- and beta-oxidation in humans: enzymology, peroxisomal metabolite transporters and peroxisomal diseases. Biochem. Soc. Trans. 29, 250\u2013267 (2001).","journal-title":"Biochem. Soc. Trans."},{"key":"748_CR83","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1172\/JCI114674","volume":"86","author":"JC Heikoop","year":"1990","unstructured":"Heikoop, J. C. et al. Rhizomelic chondrodysplasia punctata. Deficiency of 3-oxoacyl-coenzyme A thiolase in peroxisomes and impaired processing of the enzyme. J. Clin. Investig. 86, 126\u2013130 (1990).","journal-title":"J. Clin. Investig."},{"key":"748_CR84","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0167-4781(91)90035-K","volume":"1090","author":"A Bout","year":"1991","unstructured":"Bout, A. et al. Characterization of the gene encoding human peroxisomal 3-oxoacyl-CoA thiolase (ACAA). No large DNA rearrangement in a thiolase-deficient patient. Biochim. Biophys. Acta 1090, 43\u201351 (1991).","journal-title":"Biochim. Biophys. Acta"},{"key":"748_CR85","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0022-3476(86)80764-8","volume":"108","author":"S Goldfischer","year":"1986","unstructured":"Goldfischer, S. et al. Pseudo-Zellweger syndrome - deficiencies in several peroxisomal oxidative activities. J. Pediatr. 108, 25\u201332 (1986).","journal-title":"J. Pediatr."},{"key":"748_CR86","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.nbd.2011.01.021","volume":"43","author":"RA Nixon","year":"2011","unstructured":"Nixon, R. A. & Yang, D. S. Autophagy failure in Alzheimer\u2019s disease\u2013locating the primary defect. Neurobiol. Dis. 43, 38\u201345 (2011).","journal-title":"Neurobiol. Dis."},{"key":"748_CR87","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/s41573-019-0036-1","volume":"18","author":"SR Bonam","year":"2019","unstructured":"Bonam, S. R., Wang, F. J. & Muller, S. Lysosomes as a therapeutic target. Nat. Rev. Drug Discov. 18, 923\u2013948 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"748_CR88","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s00401-014-1379-7","volume":"129","author":"A Peric","year":"2015","unstructured":"Peric, A. & Annaert, W. Early etiology of Alzheimer\u2019s disease: tipping the balance toward autophagy or endosomal dysfunction? Acta Neuropathol. 129, 363\u2013381 (2015).","journal-title":"Acta Neuropathol."},{"key":"748_CR89","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1046\/j.1471-4159.1999.0721832.x","volume":"72","author":"AC LeBlanc","year":"1999","unstructured":"LeBlanc, A. C. & Goodyer, C. G. Role of endoplasmic reticulum, endosomal-lysosomal compartments, and microtubules in amyloid precursor protein metabolism of human neurons. J. Neurochem. 72, 1832\u20131842 (1999).","journal-title":"J. Neurochem."},{"key":"748_CR90","doi-asserted-by":"publisher","first-page":"4027","DOI":"10.1073\/pnas.1219454110","volume":"110","author":"S Nabavi","year":"2013","unstructured":"Nabavi, S. et al. Metabotropic NMDA receptor function is required for NMDA receptor-dependent long-term depression. Proc. Natl Acad. Sci. USA 110, 4027\u20134032 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"748_CR91","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.ceca.2011.02.001","volume":"49","author":"L Texido","year":"2011","unstructured":"Texido, L., Martin-Satue, M., Alberdi, E., Solsona, C. & Matute, C. Amyloid beta peptide oligomers directly activate NMDA receptors. Cell Calcium 49, 184\u2013190 (2011).","journal-title":"Cell Calcium"},{"key":"748_CR92","doi-asserted-by":"publisher","first-page":"7349","DOI":"10.1523\/JNEUROSCI.0037-15.2015","volume":"35","author":"LL Li","year":"2015","unstructured":"Li, L. L. et al. Unexpected heterodivalent recruitment of NOS1AP to nNOS reveals multiple sites for pharmacological intervention in neuronal disease models. J. Neurosci. 35, 7349\u20137364 (2015).","journal-title":"J. Neurosci."},{"key":"748_CR93","doi-asserted-by":"publisher","first-page":"252","DOI":"10.3389\/fncel.2014.00252","volume":"8","author":"MJ Courtney","year":"2014","unstructured":"Courtney, M. J., Li, L. L. & Lai, Y. Y. Mechanisms of NOS1AP action on NMDA receptor-nNOS signaling. Front. Cell. Neurosci. 8, 252 (2014).","journal-title":"Front. Cell. Neurosci."},{"key":"748_CR94","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1126\/science.6093256","volume":"226","author":"RP Simon","year":"1984","unstructured":"Simon, R. P., Swan, J. H., Griffiths, T. & Meldrum, B. S. Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 226, 850\u2013852 (1984).","journal-title":"Science"},{"key":"748_CR95","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.neuron.2014.03.030","volume":"82","author":"MP Parsons","year":"2014","unstructured":"Parsons, M. P. & Raymond, L. A. Extrasynaptic NMDA receptor involvement in central nervous system disorders. Neuron 82, 279\u2013293 (2014).","journal-title":"Neuron"},{"key":"748_CR96","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/s41593-019-0419-y","volume":"22","author":"G Gunner","year":"2019","unstructured":"Gunner, G. et al. Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling. Nat. Neurosci. 22, 1075\u20131088 (2019).","journal-title":"Nat. Neurosci."},{"key":"748_CR97","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.jalz.2011.03.004","volume":"7","author":"CR Jack Jr.","year":"2011","unstructured":"Jack, C. R. Jr. et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement. 7, 257\u2013262 (2011).","journal-title":"Alzheimers Dement."},{"key":"748_CR98","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.jalz.2011.04.003","volume":"7","author":"ZS Khachaturian","year":"2011","unstructured":"Khachaturian, Z. S. Revised criteria for diagnosis of Alzheimer\u2019s disease: National Institute on Aging-Alzheimer\u2019s Association diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement. 7, 253\u2013256 (2011).","journal-title":"Alzheimers Dement."},{"key":"748_CR99","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1212\/WNL.34.7.939","volume":"34","author":"G McKhann","year":"1984","unstructured":"McKhann, G. et al. Clinical diagnosis of Alzheimer\u2019s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer\u2019s disease. Neurology 34, 939\u2013944 (1984).","journal-title":"Neurology"},{"key":"748_CR100","doi-asserted-by":"publisher","first-page":"1604 e1607","DOI":"10.1016\/j.neurobiolaging.2014.10.009","volume":"36","author":"R Bi","year":"2015","unstructured":"Bi, R. et al. Mitochondrial DNA haplogroup B5 confers genetic susceptibility to Alzheimer\u2019s disease in Han Chinese. Neurobiol. Aging 36, 1604 e1607\u20131604 e1616 (2015).","journal-title":"Neurobiol. Aging"},{"key":"748_CR101","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.jgg.2017.05.005","volume":"44","author":"J Tang","year":"2017","unstructured":"Tang, J. et al. Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia. J. Genet. Genomics 44, 295\u2013306 (2017).","journal-title":"J. Genet. Genomics"},{"key":"748_CR102","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114\u20132120 (2014).","journal-title":"Bioinformatics"},{"key":"748_CR103","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"748_CR104","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491\u2013498 (2011).","journal-title":"Nat. Genet."},{"key":"748_CR105","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1002\/humu.22932","volume":"37","author":"X Liu","year":"2015","unstructured":"Liu, X., Wu, C., Li, C. & Boerwinkle, E. dbNSFP v3.0: a one-stop database of functional predictions and annotations for human non-synonymous and splice site SNVs. Hum. Mutat. 37, 235\u2013241 (2015).","journal-title":"Hum. Mutat."},{"key":"748_CR106","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1080\/15548627.2017.1332549","volume":"13","author":"LY Su","year":"2017","unstructured":"Su, L. Y. et al. Atg5- and Atg7-dependent autophagy in dopaminergic neurons regulates cellular and behavioral responses to morphine. Autophagy 13, 1496\u20131511 (2017).","journal-title":"Autophagy"},{"key":"748_CR107","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.4049\/jimmunol.2000376","volume":"205","author":"L Xu","year":"2020","unstructured":"Xu, L. et al. Tupaia MAVS is a dual target during hepatitis C virus infection for innate immune evasion and viral replication via NF-kappaB. J. Immunol. 205, 2091\u20132099 (2020).","journal-title":"J. Immunol."},{"key":"748_CR108","doi-asserted-by":"publisher","first-page":"3419","DOI":"10.4049\/jimmunol.2000740","volume":"205","author":"YL Yao","year":"2020","unstructured":"Yao, Y. L. et al. Tupaia OASL1 promotes cellular antiviral immune responses by recruiting MDA5 to MAVS. J. Immunol. 205, 3419\u20133428 (2020).","journal-title":"J. Immunol."},{"key":"748_CR109","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1172\/JCI66771","volume":"125","author":"M Krauthausen","year":"2015","unstructured":"Krauthausen, M. et al. CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer\u2019s disease model. J. Clin. Investig. 125, 365\u2013378 (2015).","journal-title":"J. Clin. Investig."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-021-00748-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-021-00748-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-021-00748-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T03:03:26Z","timestamp":1675652606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-021-00748-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":109,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["748"],"URL":"https:\/\/doi.org\/10.1038\/s41392-021-00748-4","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]},"assertion":[{"value":"5 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"325"}}