{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:05:52Z","timestamp":1790996752533,"version":"4.1.0"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"publisher","award":["2040-00047B"],"award-info":[{"award-number":["2040-00047B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Disease"],"published-print":{"date-parts":[[2024,11]]},"DOI":"10.1016\/j.nbd.2024.106728","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T04:14:04Z","timestamp":1730952844000},"page":"106728","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["LRRK2 and RAB8A regulate cell death after lysosomal damage in macrophages through cholesterol-related pathways"],"prefix":"10.1016","volume":"202","author":[{"given":"Josefine Fussing","family":"Tengberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tau","family":"Benned-Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nbd.2024.106728_bb0005","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/mds.27818","article-title":"Higher urine bis(Monoacylglycerol)phosphate levels in LRRK2 G2019S mutation carriers: implications for therapeutic development","volume":"35","author":"Alcalay","year":"2020","journal-title":"Mov. Disord."},{"key":"10.1016\/j.nbd.2024.106728_bb0010","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abb2454","article-title":"LRRK2 mediates tubulation and vesicle sorting from lysosomes","volume":"6","author":"Bonet-Ponce","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.nbd.2024.106728_bb0015","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.aag1417","article-title":"Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-pick C1 signaling complex","volume":"355","author":"Castellano","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.nbd.2024.106728_bb0020","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/ng.3955","article-title":"A meta-analysis of genome-wide association studies identifies 17 new Parkinson\u2019s disease risk loci","volume":"49","author":"Chang","year":"2017","journal-title":"Nat. Genet."},{"key":"10.1016\/j.nbd.2024.106728_bb0025","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.2337\/db17-0077","article-title":"Rab8a deficiency in skeletal muscle causes hyperlipidemia and Hepatosteatosis by impairing muscle lipid uptake and storage","volume":"66","author":"Chen","year":"2017","journal-title":"Diabetes"},{"key":"10.1016\/j.nbd.2024.106728_bb0030","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.3390\/ijms22031045","article-title":"Genetic and environmental factors influence the pleomorphy of LRRK2 parkinsonism","volume":"22","author":"Chittoor-Vinod","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.nbd.2024.106728_bb0035","article-title":"LRRK2 exonic variants associated with Parkinson\u2019s disease augment phosphorylation levels for LRRK2-Ser1292 and Rab10-Thr73","author":"Christensen","year":"2018","journal-title":"bioRxiv"},{"key":"10.1016\/j.nbd.2024.106728_bb0040","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1152\/physrev.00022.2010","article-title":"What genetics tells us about the causes and mechanisms of Parkinson\u2019s disease","volume":"91","author":"Corti","year":"2011","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.nbd.2024.106728_bb0045","doi-asserted-by":"crossref","first-page":"E9115","DOI":"10.1073\/pnas.1812196115","article-title":"LRRK2 and its substrate Rab GTPases are sequentially targeted onto stressed lysosomes and maintain their homeostasis","volume":"115","author":"Eguchi","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.nbd.2024.106728_bb0050","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.3233\/JPD-202138","article-title":"LRRK2 and the endolysosomal system in Parkinson\u2019s disease","volume":"10","author":"Erb","year":"2020","journal-title":"J. Parkinsons Dis."},{"key":"10.1016\/j.nbd.2024.106728_bb0055","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0062143","article-title":"Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis","volume":"8","author":"Freeman","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.nbd.2024.106728_bb0060","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41531-023-00482-4","article-title":"Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson\u2019s disease","volume":"9","author":"Gomes","year":"2023","journal-title":"NPJ Parkinsons Dis."},{"key":"10.1016\/j.nbd.2024.106728_bb0065","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41586-021-04064-3","article-title":"The power of genetic diversity in genome-wide association studies of lipids","volume":"600","author":"Graham","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.nbd.2024.106728_bb0070","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2020104494","article-title":"LRRK2 activation controls the repair of damaged endomembranes in macrophages","volume":"39","author":"Herbst","year":"2020","journal-title":"EMBO J."},{"key":"10.1016\/j.nbd.2024.106728_bb0075","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41588-018-0064-5","article-title":"A large electronic-health-record-based genome-wide study of serum lipids","volume":"50","author":"Hoffmann","year":"2018","journal-title":"Nat. Genet."},{"key":"10.1016\/j.nbd.2024.106728_bb0080","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1002\/mds.28037","article-title":"Rare variants in specific lysosomal genes are associated with Parkinson\u2019s disease","volume":"35","author":"Hopfner","year":"2020","journal-title":"Mov. Disord."},{"key":"10.1016\/j.nbd.2024.106728_bb0085","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abj2658","article-title":"Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson\u2019s disease","volume":"14","author":"Jennings","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.nbd.2024.106728_bb0090","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/mds.29297","article-title":"LRRK2 inhibition by BIIB122 in healthy participants and patients with Parkinson\u2019s disease","volume":"38","author":"Jennings","year":"2023","journal-title":"Mov. Disord."},{"key":"10.1016\/j.nbd.2024.106728_bb0095","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.molcel.2018.03.009","article-title":"Galectins control mTOR in response to endomembrane damage","volume":"70","author":"Jia","year":"2018","journal-title":"Mol. Cell"},{"key":"10.1016\/j.nbd.2024.106728_bb0100","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1042\/BCJ20200458","article-title":"Endogenous Rab29 does not impact basal or stimulated LRRK2 pathway activity","volume":"477","author":"Kalogeropulou","year":"2020","journal-title":"Biochem. J."},{"key":"10.1016\/j.nbd.2024.106728_bb0105","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.devcel.2013.09.016","article-title":"LDL cholesterol recycles to the plasma membrane via a Rab8a-Myosin5b-actin-dependent membrane transport route","volume":"27","author":"Kanerva","year":"2013","journal-title":"Dev. Cell"},{"key":"10.1016\/j.nbd.2024.106728_bb0110","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1515\/hsz-2016-0252","article-title":"Lysosomes in programmed cell death pathways: from initiators to amplifiers","volume":"398","author":"Kav\u010di\u010d","year":"2017","journal-title":"Biol. Chem."},{"key":"10.1016\/j.nbd.2024.106728_bb0115","doi-asserted-by":"crossref","first-page":"105081","DOI":"10.1016\/j.nbd.2020.105081","article-title":"Roles of lysosomotropic agents on LRRK2 activation and Rab10 phosphorylation","volume":"145","author":"Kuwahara","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.nbd.2024.106728_bb0120","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1091\/mbc.e06-07-0575","article-title":"Rab8-dependent recycling promotes endosomal cholesterol removal in normal and sphingolipidosis cells","volume":"18","author":"Linder","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.nbd.2024.106728_bb0125","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1161\/ATVBAHA.108.179481","article-title":"Rab8 regulates ABCA1 cell surface expression and facilitates cholesterol efflux in primary human macrophages","volume":"29","author":"Linder","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.nbd.2024.106728_bb0130","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.12177","article-title":"Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection","volume":"4","author":"Lu","year":"2015","journal-title":"Elife"},{"key":"10.1016\/j.nbd.2024.106728_bb0135","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1038\/ncomms5407","article-title":"Rab8a interacts directly with PI3Kgamma to modulate TLR4-driven PI3K and mTOR signalling","volume":"5","author":"Luo","year":"2014","journal-title":"Nat. Commun."},{"key":"10.1016\/j.nbd.2024.106728_bb0140","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13024-018-0235-y","article-title":"Parkinson disease-associated mutations in LRRK2 cause centrosomal defects via Rab8a phosphorylation","volume":"13","author":"Madero-P\u00e9rez","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.nbd.2024.106728_bib256","article-title":"LRRK2 Kinase Activity Regulates Parkinson\u2019s Disease-Relevant Lipids at the","volume":"bioRxiv","author":"Maloney","year":"2022","journal-title":"Lysosome."},{"key":"10.1016\/j.nbd.2024.106728_bb0145","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.tcb.2020.02.007","article-title":"Cholesterol handling in lysosomes and beyond","volume":"30","author":"Meng","year":"2020","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.nbd.2024.106728_bb0150","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","article-title":"Identification of novel risk loci, causal insights, and heritable risk for Parkinson\u2019s disease: a meta-analysis of genome-wide association studies","volume":"18","author":"Nalls","year":"2019","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.nbd.2024.106728_bb0155","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2020106162","article-title":"LRRK2 to the rescue of damaged endomembranes","volume":"39","author":"Radulovic","year":"2020","journal-title":"EMBO J."},{"key":"10.1016\/j.nbd.2024.106728_bb0160","doi-asserted-by":"crossref","DOI":"10.15252\/embj.201899753","article-title":"ESCRT-mediated lysosome repair precedes lysophagy and promotes cell survival","volume":"37","author":"Radulovic","year":"2018","journal-title":"EMBO J."},{"key":"10.1016\/j.nbd.2024.106728_bb0165","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2022112677","article-title":"Cholesterol transfer via endoplasmic reticulum contacts mediates lysosome damage repair","volume":"41","author":"Radulovic","year":"2022","journal-title":"EMBO J."},{"key":"10.1016\/j.nbd.2024.106728_bb0170","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.mito.2014.06.006","article-title":"Lysosomal membrane permeabilization in cell death: concepts and challenges","volume":"19","author":"Repnik","year":"2014","journal-title":"Mitochondrion"},{"key":"10.1016\/j.nbd.2024.106728_bb0175","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S1474-4422(11)70175-2","article-title":"Association of LRRK2 exonic variants with susceptibility to Parkinson\u2019s disease: a case-control study","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.nbd.2024.106728_bb0180","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR signaling in growth, metabolism, and disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.nbd.2024.106728_bb0185","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00109-023-02411-7","article-title":"PRKAA2, MTOR, and TFEB in the regulation of lysosomal damage response and autophagy","volume":"102","author":"Shariq","year":"2024","journal-title":"J. Mol. Med. (Berl)"},{"key":"10.1016\/j.nbd.2024.106728_bb0190","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fnagi.2019.00013","article-title":"A comprehensive analysis of population differences in LRRK2 variant distribution in Parkinson\u2019s disease","volume":"11","author":"Shu","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.nbd.2024.106728_bb0195","doi-asserted-by":"crossref","DOI":"10.1126\/science.aar5078","article-title":"Triggered recruitment of ESCRT machinery promotes endolysosomal repair","volume":"360","author":"Skowyra","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.nbd.2024.106728_bb0200","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.12813","article-title":"Phosphoproteomics reveals that Parkinson\u2019s disease kinase LRRK2 regulates a subset of Rab GTPases","volume":"5","author":"Steger","year":"2016","journal-title":"eLife"},{"key":"10.1016\/j.nbd.2024.106728_bb0205","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.31012","article-title":"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis","volume":"6","author":"Steger","year":"2017","journal-title":"eLife"},{"key":"10.1016\/j.nbd.2024.106728_bb0210","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41586-022-05164-4","article-title":"A phosphoinositide signalling pathway mediates rapid lysosomal repair","volume":"609","author":"Tan","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.nbd.2024.106728_bb0215","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1073\/pnas.87.1.83","article-title":"Mechanism of L-leucyl-L-leucine methyl ester-mediated killing of cytotoxic lymphocytes: dependence on a lysosomal thiol protease, dipeptidyl peptidase I, that is enriched in these cells","volume":"87","author":"Thiele","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.nbd.2024.106728_bb0220","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-10501-z","article-title":"Selective LRRK2 kinase inhibition reduces phosphorylation of endogenous Rab10 and Rab12 in human peripheral mononuclear blood cells","volume":"7","author":"Thirstrup","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.nbd.2024.106728_bb0225","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/21541248.2019.1587278","article-title":"Guanine nucleotide exchange factors activate Rab8a for toll-like receptor signalling","volume":"12","author":"Tong","year":"2021","journal-title":"Small GTPases"},{"key":"10.1016\/j.nbd.2024.106728_bb0230","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202013257","article-title":"Urinary proteome profiling for stratifying patients with familial Parkinson\u2019s disease","volume":"13","author":"Virreira Winter","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.nbd.2024.106728_bb0235","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1074\/jbc.M116.766337","article-title":"Small GTPase Rab8a-recruited phosphatidylinositol 3-kinase gamma regulates signaling and cytokine outputs from endosomal toll-like receptors","volume":"292","author":"Wall","year":"2017","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.nbd.2024.106728_bb0240","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1111\/tra.12613","article-title":"Lysosomal membrane permeabilization and cell death","volume":"19","author":"Wang","year":"2018","journal-title":"Traffic"},{"key":"10.1016\/j.nbd.2024.106728_bb0245","article-title":"Understanding LRRK2 kinase activity in preclinical models and human subjects through quantitative analysis of LRRK2 and pT73 Rab10","volume":"11","author":"Wang","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.nbd.2024.106728_bb0250","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/s41419-018-1227-0","article-title":"Lysosomotropic drugs activate TFEB via lysosomal membrane fluidization and consequent inhibition of mTORC1 activity","volume":"9","author":"Zhitomirsky","year":"2018","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.nbd.2024.106728_bb0255","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ajhg.2011.06.008","article-title":"A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset parkinson disease","volume":"89","author":"Zimprich","year":"2011","journal-title":"Am. J. Hum. Genet."}],"container-title":["Neurobiology of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996124003309?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996124003309?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T10:28:40Z","timestamp":1733135320000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969996124003309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":52,"alternative-id":["S0969996124003309"],"URL":"https:\/\/doi.org\/10.1016\/j.nbd.2024.106728","relation":{},"ISSN":["0969-9961"],"issn-type":[{"value":"0969-9961","type":"print"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"LRRK2 and RAB8A regulate cell death after lysosomal damage in macrophages through cholesterol-related pathways","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nbd.2024.106728","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"106728"}}