{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:58:37Z","timestamp":1793066317136,"version":"4.5.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"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":["Mol Neurodegeneration"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Variants in the\n                      <jats:italic>CTSB<\/jats:italic>\n                      gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson\u2019s disease (PD). However, neither the specific\n                      <jats:italic>CTSB<\/jats:italic>\n                      variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we conducted genetic analyses of the association between common and rare\n                      <jats:italic>CTSB<\/jats:italic>\n                      variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines, induced pluripotent stem cell-derived dopaminergic neurons and midbrain organoids and assessed lysosomal activity and the handling of aggregated synuclein fibrils.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by\n                      <jats:italic>GBA1<\/jats:italic>\n                      ) activity, and leads to an accumulation of lysosomal content. In cell lines, reduction of\n                      <jats:italic>CTSB<\/jats:italic>\n                      gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas\n                      <jats:italic>CTSB<\/jats:italic>\n                      gene activation enhances fibril clearance. In midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13024-024-00779-9","type":"journal-article","created":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T23:24:26Z","timestamp":1732490666000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["The Parkinson\u2019s disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons"],"prefix":"10.1186","volume":"19","author":[{"given":"Jace","family":"Jones-Tabah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Karpilovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Senkevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislaine","family":"Deyab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Pietrantonio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Goiran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Cousineau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Nikanorova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Goldsmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"del Cid Pellitero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol X.-Q.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narges","family":"Abdian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamil","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Ruskey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farnaz","family":"Asayesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Spiegelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Fahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Waters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oury","family":"Monchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Dauvilliers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Dupr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Miliukhina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla","family":"Timofeeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Emelyanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofya","family":"Pchelina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Greenbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Hassin-Baer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy N.","family":"Alcalay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austen","family":"Milnerwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Durcan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziv","family":"Gan-Or","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5520-6239","authenticated-orcid":false,"given":"Edward A.","family":"Fon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"issue":"2","key":"779_CR1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41583-020-00416-6","volume":"22","author":"MB Fares","year":"2021","unstructured":"Fares MB, Jagannath S, Lashuel HA. Reverse engineering Lewy bodies: how far have we come and how far can we go? Nat Rev Neurosci. 2021;22(2):111\u201331. https:\/\/doi.org\/10.1038\/s41583-020-00416-6.","journal-title":"Nat Rev Neurosci"},{"issue":"9440","key":"779_CR2","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/s0140-6736(04)17104-3","volume":"364","author":"P Ib\u00e1\u00f1ez","year":"2004","unstructured":"Ib\u00e1\u00f1ez P, Bonnet AM, D\u00e9barges B, et al. Causal relation between alpha-synuclein gene duplication and familial Parkinson\u2019s disease. Lancet (London, England). 2004;364(9440):1169\u201371. https:\/\/doi.org\/10.1016\/s0140-6736(04)17104-3.","journal-title":"Lancet (London, England)."},{"issue":"1","key":"779_CR3","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/ana.25274","volume":"84","author":"L Pihlstr\u00f8m","year":"2018","unstructured":"Pihlstr\u00f8m L, Blauwendraat C, Cappelletti C, et al. A comprehensive analysis of SNCA-related genetic risk in sporadic parkinson disease. Ann Neurol. 2018;84(1):117\u201329. https:\/\/doi.org\/10.1002\/ana.25274.","journal-title":"Ann Neurol"},{"issue":"8","key":"779_CR4","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1523\/JNEUROSCI.3809-03.2004","volume":"24","author":"L He-Jin","year":"2004","unstructured":"He-Jin L, Farnaz K, Smita P, Seung-Jae L. Clearance of \u03b1-Synuclein oligomeric intermediates via the lysosomal degradation pathway. J Neurosci. 2004;24(8):1888. https:\/\/doi.org\/10.1523\/JNEUROSCI.3809-03.2004.","journal-title":"J Neurosci"},{"issue":"18","key":"779_CR5","doi-asserted-by":"publisher","first-page":"13621","DOI":"10.1074\/jbc.M109.074617","volume":"285","author":"SK Mak","year":"2010","unstructured":"Mak SK, McCormack AL, Manning-Bo\u011f AB, Cuervo AM, Di Monte DA. Lysosomal degradation of \u03b1-Synuclein in Vivo*. J Biol Chem. 2010;285(18):13621\u20139. https:\/\/doi.org\/10.1074\/jbc.M109.074617.","journal-title":"J Biol Chem"},{"issue":"35","key":"779_CR6","doi-asserted-by":"publisher","first-page":"23542","DOI":"10.1074\/jbc.M801992200","volume":"283","author":"T Vogiatzi","year":"2008","unstructured":"Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L. Wild type alpha-Synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J Biol Chem. 2008;283(35):23542\u201356. https:\/\/doi.org\/10.1074\/jbc.M801992200.","journal-title":"J Biol Chem"},{"key":"779_CR7","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.parkreldis.2019.11.015","volume":"73","author":"K Senkevich","year":"2020","unstructured":"Senkevich K, Gan-Or Z. Autophagy lysosomal pathway dysfunction in Parkinson\u2019s disease; evidence from human genetics. Parkinsonism Relat Disord. 2020;73:60\u201371. https:\/\/doi.org\/10.1016\/j.parkreldis.2019.11.015.","journal-title":"Parkinsonism Relat Disord."},{"key":"779_CR8","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.arr.2016.04.010","volume":"32","author":"V Stoka","year":"2016","unstructured":"Stoka V, Turk V, Turk B. Lysosomal cathepsins and their regulation in aging and neurodegeneration. Ageing Res Rev. 2016;32:22\u201337. https:\/\/doi.org\/10.1016\/j.arr.2016.04.010.","journal-title":"Ageing Res Rev."},{"issue":"12","key":"779_CR9","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/s1474-4422(19)30320-5","volume":"18","author":"MA Nalls","year":"2019","unstructured":"Nalls MA, Blauwendraat C, Vallerga CL, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson\u2019s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019;18(12):1091\u2013102. https:\/\/doi.org\/10.1016\/s1474-4422(19)30320-5.","journal-title":"Lancet Neurol"},{"issue":"1","key":"779_CR10","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1093\/brain\/awz350","volume":"143","author":"C Blauwendraat","year":"2020","unstructured":"Blauwendraat C, Reed X, Krohn L, et al. Genetic modifiers of risk and age at onset in GBA associated Parkinson\u2019s disease and Lewy body dementia. Brain J Neurol. 2020;143(1):234\u201348. https:\/\/doi.org\/10.1093\/brain\/awz350.","journal-title":"Brain J Neurol"},{"issue":"1","key":"779_CR11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40035-023-00363-z","volume":"12","author":"A Drobny","year":"2023","unstructured":"Drobny A, Boros FA, Balta D, et al. Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models. Transl Neurodegen. 2023;12(1):31. https:\/\/doi.org\/10.1186\/s40035-023-00363-z.","journal-title":"Transl Neurodegen."},{"key":"779_CR12","doi-asserted-by":"publisher","first-page":"442","DOI":"10.3389\/fnins.2020.00442","volume":"14","author":"A Sanyal","year":"2020","unstructured":"Sanyal A, Novis HS, Gasser E, Lin S, LaVoie MJ. LRRK2 kinase inhibition rescues deficits in lysosome function due to Heterozygous GBA1 expression in human iPSC-derived neurons. Front Neurosci. 2020;14:442. https:\/\/doi.org\/10.3389\/fnins.2020.00442.","journal-title":"Front Neurosci"},{"issue":"7","key":"779_CR13","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1073\/pnas.1520335113","volume":"113","author":"JR Mazzulli","year":"2016","unstructured":"Mazzulli JR, Zunke F, Isacson O, Studer L, Krainc D. \u03b1-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models. Proc Natl Acad Sci USA. 2016;113(7):1931\u20136. https:\/\/doi.org\/10.1073\/pnas.1520335113.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"13","key":"779_CR14","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1016\/j.cell.2022.05.021","volume":"185","author":"M Hu","year":"2022","unstructured":"Hu M, Li P, Wang C, et al. Parkinson\u2019s disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes. Cell. 2022;185(13):2292-2308.e20. https:\/\/doi.org\/10.1016\/j.cell.2022.05.021.","journal-title":"Cell."},{"issue":"9","key":"779_CR15","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.1073\/pnas.1616332114","volume":"114","author":"S Jinn","year":"2017","unstructured":"Jinn S, Drolet RE, Cramer PE, et al. TMEM175 deficiency impairs lysosomal and mitochondrial function and increases \u03b1-synuclein aggregation. Proc Natl Acad Sci. 2017;114(9):2389\u201394. https:\/\/doi.org\/10.1073\/pnas.1616332114.","journal-title":"Proc Natl Acad Sci"},{"issue":"21","key":"779_CR16","doi-asserted-by":"publisher","first-page":"6013","DOI":"10.1093\/hmg\/ddv314","volume":"24","author":"AG Henry","year":"2015","unstructured":"Henry AG, Aghamohammadzadeh S, Samaroo H, et al. Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression. Hum Mol Genet. 2015;24(21):6013\u201328. https:\/\/doi.org\/10.1093\/hmg\/ddv314.","journal-title":"Hum Mol Genet"},{"issue":"31","key":"779_CR17","doi-asserted-by":"publisher","first-page":"e2303789120","DOI":"10.1073\/pnas.2303789120","volume":"120","author":"N Yadavalli","year":"2023","unstructured":"Yadavalli N, Ferguson SM. LRRK2 suppresses lysosome degradative activity in macrophages and microglia through MiT-TFE transcription factor inhibition. Proc Natl Acad Sci. 2023;120(31);e2303789120. https:\/\/doi.org\/10.1073\/pnas.2303789120.","journal-title":"Proc Natl Acad Sci."},{"issue":"25","key":"779_CR18","doi-asserted-by":"publisher","first-page":"9973","DOI":"10.1074\/jbc.RA119.008930","volume":"294","author":"RP McGlinchey","year":"2019","unstructured":"McGlinchey RP, Lacy SM, Huffer KE, Tayebi N, Sidransky E, Lee JC. C-terminal alpha-synuclein truncations are linked to cysteine cathepsin activity in Parkinson\u2019s disease. J Biol Chem. 2019;294(25):9973\u201384. https:\/\/doi.org\/10.1074\/jbc.RA119.008930.","journal-title":"J Biol Chem"},{"issue":"30","key":"779_CR19","doi-asserted-by":"publisher","first-page":"9322","DOI":"10.1073\/pnas.1500937112","volume":"112","author":"RP McGlinchey","year":"2015","unstructured":"McGlinchey RP, Lee JC. Cysteine cathepsins are essential in lysosomal degradation of \u03b1-synuclein. Proc Natl Acad Sci. 2015;112(30):9322\u20137. https:\/\/doi.org\/10.1073\/pnas.1500937112.","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"779_CR20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13024-023-00621-8","volume":"18","author":"PJ Sampognaro","year":"2023","unstructured":"Sampognaro PJ, Arya S, Knudsen GM, et al. Mutations in \u03b1-synuclein, TDP-43 and tau prolong protein half-life through diminished degradation by lysosomal proteases. Mol Neurodegen. 2023;18(1):29. https:\/\/doi.org\/10.1186\/s13024-023-00621-8.","journal-title":"Mol Neurodegen."},{"key":"779_CR21","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.nbd.2014.10.011","volume":"73","author":"A Tsujimura","year":"2015","unstructured":"Tsujimura A, Taguchi K, Watanabe Y, et al. Lysosomal enzyme cathepsin B enhances the aggregate forming activity of exogenous \u03b1-synuclein fibrils. Neurobiol Dis. 2015;73:244\u201353. https:\/\/doi.org\/10.1016\/j.nbd.2014.10.011.","journal-title":"Neurobiol Dis"},{"issue":"4","key":"779_CR22","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1111\/jnc.13743","volume":"140","author":"AN Sacino","year":"2017","unstructured":"Sacino AN, Brooks MM, Chakrabarty P, et al. Proteolysis of \u03b1-synuclein fibrils in the lysosomal pathway limits induction of inclusion pathology. J Neurochem. 2017;140(4):662\u201378. https:\/\/doi.org\/10.1111\/jnc.13743.","journal-title":"J Neurochem"},{"issue":"51","key":"779_CR23","doi-asserted-by":"publisher","first-page":"17497","DOI":"10.1074\/jbc.RA120.013428","volume":"295","author":"SJ Guiney","year":"2020","unstructured":"Guiney SJ, Adlard PA, Lei P, et al. Fibrillar \u03b1-synuclein toxicity depends on functional lysosomes. J Biol Chem. 2020;295(51):17497\u2013513. https:\/\/doi.org\/10.1074\/jbc.RA120.013428.","journal-title":"J Biol Chem"},{"issue":"1","key":"779_CR24","doi-asserted-by":"publisher","first-page":"e55375","DOI":"10.1371\/journal.pone.0055375","volume":"8","author":"G Codolo","year":"2013","unstructured":"Codolo G, Plotegher N, Pozzobon T, et al. Triggering of inflammasome by aggregated \u03b1\u2013Synuclein, an inflammatory response in Synucleinopathies. PLoS ONE. 2013;8(1);e55375. https:\/\/doi.org\/10.1371\/journal.pone.0055375.","journal-title":"PLoS ONE"},{"issue":"4","key":"779_CR25","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41419-023-05786-0","volume":"14","author":"Z Xie","year":"2023","unstructured":"Xie Z, Zhao M, Yan C, et al. Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways. Cell Death Dis. 2023;14(4):255. https:\/\/doi.org\/10.1038\/s41419-023-05786-0.","journal-title":"Cell Death Dis."},{"issue":"1","key":"779_CR26","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","volume":"88","author":"J Yang","year":"2011","unstructured":"Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet. 2011;88(1):76\u201382. https:\/\/doi.org\/10.1016\/j.ajhg.2010.11.011.","journal-title":"Am J Hum Genet"},{"issue":"3","key":"779_CR27","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559\u201375. https:\/\/doi.org\/10.1086\/519795.","journal-title":"Am J Hum Genet"},{"issue":"10","key":"779_CR28","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1093\/bioinformatics\/btw018","volume":"32","author":"C Benner","year":"2016","unstructured":"Benner C, Spencer CC, Havulinna AS, Salomaa V, Ripatti S, Pirinen M. FINEMAP: efficient variable selection using summary data from genome-wide association studies. Bioinformatics (Oxford, England). 2016;32(10):1493\u2013501. https:\/\/doi.org\/10.1093\/bioinformatics\/btw018.","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"5","key":"779_CR29","doi-asserted-by":"publisher","first-page":"e1004383","DOI":"10.1371\/journal.pgen.1004383","volume":"10","author":"C Giambartolomei","year":"2014","unstructured":"Giambartolomei C, Vukcevic D, Schadt EE, et al. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet. 2014;10(5):e1004383. https:\/\/doi.org\/10.1371\/journal.pgen.1004383.","journal-title":"PLoS Genet"},{"key":"779_CR30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.bone.2018.05.012","volume":"113","author":"XH Meng","year":"2018","unstructured":"Meng XH, Chen XD, Greenbaum J, et al. Integration of summary data from GWAS and eQTL studies identified novel causal BMD genes with functional predictions. Bone. 2018;113:41\u20138. https:\/\/doi.org\/10.1016\/j.bone.2018.05.012.","journal-title":"Bone"},{"issue":"3","key":"779_CR31","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1136\/jnnp.55.3.181","volume":"55","author":"AJ Hughes","year":"1992","unstructured":"Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson\u2019s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181\u20134. https:\/\/doi.org\/10.1136\/jnnp.55.3.181.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"12","key":"779_CR32","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","volume":"30","author":"RB Postuma","year":"2015","unstructured":"Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson\u2019s disease. Movement Disord Off J Movement Disord Soc. 2015;30(12):1591\u2013601. https:\/\/doi.org\/10.1002\/mds.26424.","journal-title":"Movement Disord Off J Movement Disord Soc"},{"key":"779_CR33","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1471-2105-15-125","volume":"15","author":"AR Carson","year":"2014","unstructured":"Carson AR, Smith EN, Matsui H, et al. Effective filtering strategies to improve data quality from population-based whole exome sequencing studies. BMC Bioinform. 2014;15:125. https:\/\/doi.org\/10.1186\/1471-2105-15-125.","journal-title":"BMC Bioinform."},{"issue":"8","key":"779_CR34","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1002\/mds.28549","volume":"36","author":"H Iwaki","year":"2021","unstructured":"Iwaki H, Leonard HL, Makarious MB, et al. Accelerating medicines partnership: Parkinson\u2019s disease. Genetic resource. Movement Disord Off J Movement Disord Soc. 2021;36(8):1795\u2013804. https:\/\/doi.org\/10.1002\/mds.28549.","journal-title":"Movement Disord Off J Movement Disord Soc."},{"issue":"2","key":"779_CR35","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1093\/brain\/awaa401","volume":"144","author":"U Rudakou","year":"2021","unstructured":"Rudakou U, Yu E, Krohn L, et al. Targeted sequencing of Parkinson\u2019s disease loci genes highlights SYT11, FGF20 and other associations. Brain J Neurol. 2021;144(2):462\u201372. https:\/\/doi.org\/10.1093\/brain\/awaa401.","journal-title":"Brain J Neurol"},{"issue":"9","key":"779_CR36","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna A, Hanna M, Banks E, et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297\u2013303. https:\/\/doi.org\/10.1101\/gr.107524.110.","journal-title":"Genome Res"},{"key":"779_CR37","doi-asserted-by":"publisher","first-page":"143.e1","DOI":"10.1016\/j.neurobiolaging.2020.03.021","volume":"93","author":"B Ouled AmarBencheikh","year":"2020","unstructured":"Ouled AmarBencheikh B, Senkevich K, Rudakou U, et al. Variants in the Niemann-Pick type C gene NPC1 are not associated with Parkinson\u2019s disease. Neurobiol Aging. 2020;93:143.e1-143.e4. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2020.03.021.","journal-title":"Neurobiol Aging."},{"issue":"4","key":"779_CR38","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1093\/biostatistics\/kxs014","volume":"13","author":"S Lee","year":"2012","unstructured":"Lee S, Wu MC, Lin X. Optimal tests for rare variant effects in sequencing association studies. Biostatistics (Oxford, England). 2012;13(4):762\u201375. https:\/\/doi.org\/10.1093\/biostatistics\/kxs014.","journal-title":"Biostatistics (Oxford, England)"},{"issue":"1","key":"779_CR39","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ajhg.2013.05.010","volume":"93","author":"S Lee","year":"2013","unstructured":"Lee S, Teslovich TM, Boehnke M, Lin X. General framework for meta-analysis of rare variants in sequencing association studies. Am J Hum Genet. 2013;93(1):42\u201353. https:\/\/doi.org\/10.1016\/j.ajhg.2013.05.010.","journal-title":"Am J Hum Genet"},{"issue":"D1","key":"779_CR40","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 GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2019;47(D1):D886-d894. https:\/\/doi.org\/10.1093\/nar\/gky1016.","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"779_CR41","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3390\/mps4030050","volume":"4","author":"CX Chen","year":"2021","unstructured":"Chen CX, Abdian N, Maussion G, et al. A multistep workflow to evaluate newly generated iPSCs and their ability to generate different cell types. Methods Protocols. 2021;4(3):50. https:\/\/doi.org\/10.3390\/mps4030050.","journal-title":"Methods Protocols."},{"key":"779_CR42","doi-asserted-by":"publisher","unstructured":"Chen X, Lauinger N, Rocha C, Rao T, Durcan TM. Generation of dopaminergic or cortical neurons from neuronal progenitors (V2.0). Zenodo. 2019. https:\/\/doi.org\/10.5281\/zenodo.3738323.","DOI":"10.5281\/zenodo.3738323"},{"issue":"6","key":"779_CR43","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1002\/sctm.18-0180","volume":"9","author":"M Jefri","year":"2020","unstructured":"Jefri M, Bell S, Peng H, et al. Stimulation of L-type calcium channels increases tyrosine hydroxylase and dopamine in ventral midbrain cells induced from somatic cells. Stem Cells Transl Med. 2020;9(6):697\u2013712. https:\/\/doi.org\/10.1002\/sctm.18-0180.","journal-title":"Stem Cells Transl Med"},{"issue":"4","key":"779_CR44","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1111\/ejn.14286","volume":"49","author":"Y Chen","year":"2019","unstructured":"Chen Y, Dolt KS, Kriek M, et al. Engineering synucleinopathy-resistant human dopaminergic neurons by CRISPR-mediated deletion of the SNCA gene. Eur J Neurosci. 2019;49(4):510\u201324. https:\/\/doi.org\/10.1111\/ejn.14286.","journal-title":"Eur J Neurosci"},{"issue":"4","key":"779_CR45","doi-asserted-by":"publisher","first-page":"fcab223","DOI":"10.1093\/braincomms\/fcab223","volume":"3","author":"NV Mohamed","year":"2021","unstructured":"Mohamed NV, Sirois J, Ramamurthy J, et al. Midbrain organoids with an SNCA gene triplication model key features of synucleinopathy. Brain Commun. 2021;3(4):fcab223. https:\/\/doi.org\/10.1093\/braincomms\/fcab223.","journal-title":"Brain Commun."},{"key":"779_CR46","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.ymeth.2021.07.008","volume":"203","author":"NV Mohamed","year":"2022","unstructured":"Mohamed NV, L\u00e9pine P, Lacalle-Aurioles M, et al. Microfabricated disk technology: Rapid scale up in midbrain organoid generation. Methods. 2022;203:465\u201377. https:\/\/doi.org\/10.1016\/j.ymeth.2021.07.008.","journal-title":"Methods"},{"key":"779_CR47","doi-asserted-by":"publisher","unstructured":"Del Cid Pellitero E, Shlaifer R, Luo W, Krahn A, Nguyen-Renou E, Maneck D-L, Rao T, Beitel L, Durcan TM, Pimentel L. Quality Control Characterization of \u03b1-Synuclein Preformed Fibrils (PFFs) (V3.0). Zenodo. 2019. https:\/\/doi.org\/10.5281\/zenodo.6524616.","DOI":"10.5281\/zenodo.6524616"},{"key":"779_CR48","doi-asserted-by":"publisher","unstructured":"Maneca D-L, Luo W, Krahn A, Del Cid Pellitero E, Shlaifer I, Nicouleau M, Pimentel L, Beitel LK, Rao T, Durcan TM. Production of Recombinant \u03b1 Synuclein Monomers and Preformed Fibrils (PFFs) (V3.0). Zenodo. 2022.\u00a0https:\/\/doi.org\/10.5281\/zenodo.6430401.","DOI":"10.5281\/zenodo.6430401"},{"issue":"11","key":"779_CR49","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1038\/s41592-020-0966-x","volume":"17","author":"N Alerasool","year":"2020","unstructured":"Alerasool N, Segal D, Lee H, Taipale M. An efficient KRAB domain for CRISPRi applications in human cells. Nat Methods. 2020;17(11):1093\u20136. https:\/\/doi.org\/10.1038\/s41592-020-0966-x.","journal-title":"Nat Methods."},{"issue":"1","key":"779_CR50","doi-asserted-by":"publisher","first-page":"ENEURO.0495","DOI":"10.1523\/ENEURO.0495-18.2019","volume":"6","author":"ES Katherine","year":"2019","unstructured":"Katherine ES, Svitlana VB, Morgan EZ, et al. A Neuron-Optimized CRISPR\/dCas9 activation system for robust and specific gene regulation. Eneuro. 2019;6(1):ENEURO.0495-18.2019. https:\/\/doi.org\/10.1523\/ENEURO.0495-18.2019.","journal-title":"Eneuro."},{"key":"779_CR51","doi-asserted-by":"publisher","first-page":"e19760","DOI":"10.7554\/eLife.19760","volume":"5","author":"MA Horlbeck","year":"2016","unstructured":"Horlbeck MA, Gilbert LA, Villalta JE, et al. Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. eLife. 2016;5:e19760. https:\/\/doi.org\/10.7554\/eLife.19760.","journal-title":"eLife."},{"issue":"6","key":"779_CR52","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1124\/molpharm.121.000290","volume":"100","author":"J Jones-Tabah","year":"2021","unstructured":"Jones-Tabah J, Martin RD, Tanny JC, Clarke PBS, H\u00e9bert TE. High-content single-cell f\u00f6rster resonance energy transfer imaging of cultured striatal neurons reveals novel cross-talk in the regulation of nuclear signaling by protein kinase a and extracellular signal-regulated kinase 1\/2. Mol Pharmacol. 2021;100(6):526\u201339. https:\/\/doi.org\/10.1124\/molpharm.121.000290.","journal-title":"Mol Pharmacol"},{"issue":"7","key":"779_CR53","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/s41592-022-01507-1","volume":"19","author":"D Ershov","year":"2022","unstructured":"Ershov D, Phan M-S, Pylv\u00e4n\u00e4inen JW, et al. TrackMate 7: integrating state-of-the-art segmentation algorithms into tracking pipelines. Nature Methods. 2022;19(7):829\u201332. https:\/\/doi.org\/10.1038\/s41592-022-01507-1.","journal-title":"Nature Methods."},{"key":"779_CR54","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ymeth.2016.09.016","volume":"115","author":"J-Y Tinevez","year":"2017","unstructured":"Tinevez J-Y, Perry N, Schindelin J, et al. TrackMate: an open and extensible platform for single-particle tracking. Methods. 2017;115:80\u201390. https:\/\/doi.org\/10.1016\/j.ymeth.2016.09.016.","journal-title":"Methods."},{"key":"779_CR55","unstructured":"Peters A, Palay SL, Webster Hd. The fine structure of the nervous system : neurons and their supporting cells. 3rd ed. New York: Oxford University Press; 1991."},{"issue":"4","key":"779_CR56","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1021\/acs.biochem.1c00684","volume":"61","author":"MC Yoon","year":"2022","unstructured":"Yoon MC, Christy MP, Phan VV, et al. Molecular Features of CA-074 pH-Dependent Inhibition of Cathepsin B. Biochemistry. 2022;61(4):228\u201338. https:\/\/doi.org\/10.1021\/acs.biochem.1c00684.","journal-title":"Biochemistry"},{"issue":"9","key":"779_CR57","doi-asserted-by":"publisher","first-page":"4971","DOI":"10.1073\/pnas.1913904117","volume":"117","author":"A-L Mahul-Mellier","year":"2020","unstructured":"Mahul-Mellier A-L, Burtscher J, Maharjan N, et al. The process of Lewy body formation, rather than simply \u03b1-synuclein fibrillization, is one of the major drivers of neurodegeneration. Proc Natl Acad Sci. 2020;117(9):4971\u201382. https:\/\/doi.org\/10.1073\/pnas.1913904117.","journal-title":"Proc Natl Acad Sci."},{"issue":"3","key":"779_CR58","doi-asserted-by":"publisher","first-page":"111102","DOI":"10.1016\/j.celrep.2022.111102","volume":"40","author":"A Bayati","year":"2022","unstructured":"Bayati A, Banks E, Han C, et al. Rapid macropinocytic transfer of \u03b1-synuclein to lysosomes. Cell Rep. 2022;40(3):111102. https:\/\/doi.org\/10.1016\/j.celrep.2022.111102.","journal-title":"Cell Rep."},{"issue":"32","key":"779_CR59","doi-asserted-by":"publisher","first-page":"13482","DOI":"10.1074\/jbc.M117.780296","volume":"292","author":"RJ Karpowicz Jr","year":"2017","unstructured":"Karpowicz RJ Jr, Haney CM, Mihaila TS, Sandler RM, Petersson EJ, Lee VM. Selective imaging of internalized proteopathic \u03b1-synuclein seeds in primary neurons reveals mechanistic insight into transmission of synucleinopathies. J Biol Chem. 2017;292(32):13482\u201397. https:\/\/doi.org\/10.1074\/jbc.M117.780296.","journal-title":"J Biol Chem"},{"issue":"14","key":"779_CR60","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1093\/hmg\/ddac047","volume":"31","author":"MJ Kim","year":"2022","unstructured":"Kim MJ, Jeong H, Krainc D. Lysosomal ceramides regulate cathepsin B-mediated processing of saposin C and glucocerebrosidase activity. Hum Mol Genet. 2022;31(14):2424\u201337. https:\/\/doi.org\/10.1093\/hmg\/ddac047.","journal-title":"Hum Mol Genet"},{"issue":"2","key":"779_CR61","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/ana.10279","volume":"52","author":"JE Duda","year":"2002","unstructured":"Duda JE, Giasson BI, Mabon ME, Lee VM, Trojanowski JQ. Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases. Ann Neurol. 2002;52(2):205\u201310. https:\/\/doi.org\/10.1002\/ana.10279.","journal-title":"Ann Neurol"},{"issue":"4","key":"779_CR62","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.4049\/jimmunol.1500509","volume":"195","author":"GM Orlowski","year":"2015","unstructured":"Orlowski GM, Colbert JD, Sharma S, Bogyo M, Robertson SA, Rock KL. Multiple cathepsins promote Pro-IL-1\u03b2 synthesis and NLRP3-mediated IL-1\u03b2 activation. J Immunol (Baltimore, Md\u202f: 1950). 2015;195(4):1685\u201397. https:\/\/doi.org\/10.4049\/jimmunol.1500509.","journal-title":"J Immunol (Baltimore, Md : 1950)."},{"issue":"1","key":"779_CR63","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S1074-5521(00)00061-2","volume":"7","author":"M Bogyo","year":"2000","unstructured":"Bogyo M, Verhelst S, Bellingard-Dubouchaud V, Toba S, Greenbaum D. Selective targeting of lysosomal cysteine proteases with radiolabeled electrophilic substrate analogs. Chem Biol. 2000;7(1):27\u201338. https:\/\/doi.org\/10.1016\/S1074-5521(00)00061-2.","journal-title":"Chem Biol"},{"issue":"12","key":"779_CR64","doi-asserted-by":"publisher","first-page":"2504","DOI":"10.1080\/15548627.2016.1239679","volume":"12","author":"SM Man","year":"2016","unstructured":"Man SM, Kanneganti TD. Regulation of lysosomal dynamics and autophagy by CTSB\/cathepsin B. Autophagy. 2016;12(12):2504\u20135. https:\/\/doi.org\/10.1080\/15548627.2016.1239679.","journal-title":"Autophagy"},{"issue":"10","key":"779_CR65","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1084\/jem.20151938","volume":"213","author":"X Qi","year":"2016","unstructured":"Qi X, Man SM, Malireddi RKS, et al. Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection. J Exp Med. 2016;213(10):2081\u201397. https:\/\/doi.org\/10.1084\/jem.20151938.","journal-title":"J Exp Med"},{"issue":"1","key":"779_CR66","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s40478-022-01468-8","volume":"10","author":"MF Altay","year":"2022","unstructured":"Altay MF, Liu AKL, Holton JL, Parkkinen L, Lashuel HA. Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders. Acta Neuropathologica Commun. 2022;10(1):163. https:\/\/doi.org\/10.1186\/s40478-022-01468-8.","journal-title":"Acta Neuropathologica Commun."},{"key":"779_CR67","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1093\/brain\/awad345","volume":"147","author":"E Yu","year":"2023","unstructured":"Yu E, Larivi\u00e8re R, Thomas RA, et al. Machine learning nominates the inositol pathway and novel genes in Parkinson\u2019s disease. Brain J Neurol. 2023;147:887. https:\/\/doi.org\/10.1093\/brain\/awad345.","journal-title":"Brain J Neurol"},{"issue":"7","key":"779_CR68","doi-asserted-by":"publisher","first-page":"119243","DOI":"10.1016\/j.bbamcr.2022.119243","volume":"1869","author":"A Drobny","year":"2022","unstructured":"Drobny A, Prieto Huarcaya S, Dobert J, et al. The role of lysosomal cathepsins in neurodegeneration: Mechanistic insights, diagnostic potential and therapeutic approaches. Biochim Biophys Acta. 2022;1869(7):119243. https:\/\/doi.org\/10.1016\/j.bbamcr.2022.119243.","journal-title":"Biochim Biophys Acta"},{"issue":"4","key":"779_CR69","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","volume":"54","author":"C Bellenguez","year":"2022","unstructured":"Bellenguez C, K\u00fc\u00e7\u00fckali F, Jansen IE, et al. New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias. Nat Genet. Apr2022;54(4):412\u201336. https:\/\/doi.org\/10.1038\/s41588-022-01024-z.","journal-title":"Nat Genet"},{"issue":"12","key":"779_CR70","doi-asserted-by":"publisher","first-page":"168023","DOI":"10.1016\/j.jmb.2023.168023","volume":"435","author":"D Chatterjee","year":"2023","unstructured":"Chatterjee D, Krainc D. Mechanisms of Glucocerebrosidase Dysfunction in Parkinson\u2019s Disease. J Mol Biol. 2023;435(12):168023. https:\/\/doi.org\/10.1016\/j.jmb.2023.168023.","journal-title":"J Mol Biol."},{"issue":"S4","key":"779_CR71","doi-asserted-by":"publisher","first-page":"e063954","DOI":"10.1002\/alz.063954","volume":"18","author":"N-P Nykanen","year":"2022","unstructured":"Nykanen N-P, Yang C, Harari O, Davis AA, Cruchaga C, Benitez BA. Pleiotropic effect of LRRK2 on Parkinson-associated proteins and processing of pathological alpha-synuclein in myeloid cells. Alzheimer\u2019s Dementia. 2022;18(S4):e063954. https:\/\/doi.org\/10.1002\/alz.063954.","journal-title":"Alzheimer's Dementia."}],"updated-by":[{"DOI":"10.1186\/s13024-024-00791-z","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000}}],"container-title":["Molecular Neurodegeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13024-024-00779-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13024-024-00779-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13024-024-00779-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T11:12:00Z","timestamp":1734520320000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularneurodegeneration.biomedcentral.com\/articles\/10.1186\/s13024-024-00779-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["779"],"URL":"https:\/\/doi.org\/10.1186\/s13024-024-00779-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.11.566693","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-3979098\/v1","asserted-by":"object"}]},"ISSN":["1750-1326"],"issn-type":[{"value":"1750-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]},"assertion":[{"value":"22 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s13024-024-00791-z","URL":"https:\/\/doi.org\/10.1186\/s13024-024-00791-z","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"88"}}