{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:29:26Z","timestamp":1790962166206,"version":"4.1.0"},"reference-count":94,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS110188"],"award-info":[{"award-number":["NS110188"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG082373"],"award-info":[{"award-number":["AG082373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG077269"],"award-info":[{"award-number":["AG077269"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["MJFF-023425"],"award-info":[{"award-number":["MJFF-023425"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Brain Research"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.brainres.2025.149785","type":"journal-article","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T18:28:30Z","timestamp":1749925710000},"page":"149785","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Regulation of LRRK2 activity by metabolic stress and heavy metal exposure"],"prefix":"10.1016","volume":"1863","author":[{"given":"Michalis","family":"Kentros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Follett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-4271","authenticated-orcid":false,"given":"Nitya","family":"Subrahmanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravindraja","family":"Chairmandurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Melachroinou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6842-6759","authenticated-orcid":false,"given":"Diane B.","family":"Re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"de Cabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Chia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6262-6661","authenticated-orcid":false,"given":"Jillian H.","family":"Kluss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Beilina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6439-0579","authenticated-orcid":false,"given":"Heather","family":"Mortiboys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2583-1578","authenticated-orcid":false,"given":"Matthew J.","family":"LaVoie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4597-9489","authenticated-orcid":false,"given":"Hardy J.","family":"Rideout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Cookson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5546-7084","authenticated-orcid":false,"given":"Adamantios","family":"Mamais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.brainres.2025.149785_b0005","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1083\/jcb.200408165","article-title":"Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells","volume":"167","author":"Ang","year":"2004","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.brainres.2025.149785_b0010","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1073\/pnas.1318306111","article-title":"Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease","volume":"111","author":"Beilina","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.brainres.2025.149785_b0015","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.1021\/bi100157u","article-title":"Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation","volume":"49","author":"Berger","year":"2010","journal-title":"Biochemistry"},{"key":"10.1016\/j.brainres.2025.149785_b0020","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1093\/hmg\/dds522","article-title":"GTPase activity regulates kinase activity and cellular phenotypes of Parkinson\u2019s disease-associated LRRK2","volume":"22","author":"Biosa","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.brainres.2025.149785_b0025","doi-asserted-by":"crossref","unstructured":"Bonet-Ponce, L., et al. LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes. bioRxiv 2020.01.23.917252 (2020) doi:10.1101\/2020.01.23.917252.","DOI":"10.1101\/2020.01.23.917252"},{"key":"10.1016\/j.brainres.2025.149785_b0030","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.tins.2017.04.001","article-title":"The role of astrocyte dysfunction in Parkinson\u2019s disease pathogenesis","volume":"40","author":"Booth","year":"2017","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.brainres.2025.149785_b0035","doi-asserted-by":"crossref","first-page":"13311","DOI":"10.1523\/JNEUROSCI.4258-07.2007","article-title":"Functional compartmentalization of endosomal trafficking for the synaptic delivery of AMPA receptors during long-term potentiation","volume":"27","author":"Brown","year":"2007","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2025.149785_b0040","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41531-023-00609-7","article-title":"Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine physiology in VPS35 p.D620N knock-in mice","volume":"9","author":"Bu","year":"2023","journal-title":"Npj Parkinsons. Dis."},{"key":"10.1016\/j.brainres.2025.149785_b0045","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.1096\/fj.14-268615","article-title":"Intercellular transfer of transferrin receptor by a contact-, Rab8-dependent mechanism involving tunneling nanotubes","volume":"29","author":"Burtey","year":"2015","journal-title":"FASEB J."},{"key":"10.1016\/j.brainres.2025.149785_b0050","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/bs.apcsb.2020.06.004","article-title":"Controlling Ser\/Thr protein phosphatase PP1 activity and function through interaction with regulatory subunits","volume":"122","author":"Casamayor","year":"2020","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"10.1016\/j.brainres.2025.149785_b0055","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.bbrc.2018.02.007","article-title":"Role of LRRK2 in manganese-induced neuroinflammation and microglial autophagy","volume":"498","author":"Chen","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.brainres.2025.149785_b0060","doi-asserted-by":"crossref","first-page":"5827","DOI":"10.1038\/ncomms6827","article-title":"Phosphorylation of LRRK2 by casein kinase 1\u03b1 regulates trans-Golgi clustering via differential interaction with ARHGEF7","volume":"5","author":"Chia","year":"2014","journal-title":"Nat. Commun."},{"key":"10.1016\/j.brainres.2025.149785_b0065","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.1523\/JNEUROSCI.2809-19.2020","article-title":"Dietary amino acids impact LRRK2-induced neurodegeneration in Parkinson\u2019s disease models","volume":"40","author":"Chittoor-Vinod","year":"2020","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2025.149785_b0070","doi-asserted-by":"crossref","first-page":"9863","DOI":"10.1074\/jbc.M114.606756","article-title":"Glucose deprivation triggers protein kinase C-dependent \u03b2-catenin proteasomal degradation","volume":"290","author":"Choi","year":"2015","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.brainres.2025.149785_b0075","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0043472","article-title":"Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers","volume":"7","author":"Civiero","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.brainres.2025.149785_b0080","first-page":"1","article-title":"LRRK2 levels in immune cells are increased in Parkinson\u2019s disease","volume":"3","author":"Cook","year":"2017","journal-title":"Npj Parkinson\u2019s Disease"},{"key":"10.1016\/j.brainres.2025.149785_b0085","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1471-4159.2010.06894.x","article-title":"The G2019S pathogenic mutation disrupts sensitivity of leucine-rich repeat kinase 2 to manganese kinase inhibition","volume":"115","author":"Covy","year":"2010","journal-title":"J. Neurochem."},{"key":"10.1016\/j.brainres.2025.149785_b0090","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1038\/s41467-018-07586-z","article-title":"ATP-dependent membrane remodeling links EHD1 functions to endocytic recycling","volume":"9","author":"Deo","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.brainres.2025.149785_b0095","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.40202","article-title":"A pathway for Parkinson\u2019s Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain","volume":"7","author":"Dhekne","year":"2018","journal-title":"Elife"},{"key":"10.1016\/j.brainres.2025.149785_b0100","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aar5429","article-title":"LRRK2 activation in idiopathic Parkinson\u2019s disease","volume":"10","author":"Di Maio","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.brainres.2025.149785_b0105","first-page":"6061","article-title":"Manganese-driven CoQ deficiency","volume":"13","author":"Diessl","year":"2022","journal-title":"Na\u1e6d Commun."},{"key":"10.1016\/j.brainres.2025.149785_b0110","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0039132","article-title":"The IkappaB kinase family phosphorylates the Parkinson\u2019s disease kinase LRRK2 at Ser935 and Ser910 during Toll-like receptor signaling","volume":"7","author":"Dzamko","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.brainres.2025.149785_b0115","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. U. S. A."},{"key":"10.1016\/j.brainres.2025.149785_b0120","doi-asserted-by":"crossref","first-page":"16933","DOI":"10.1523\/JNEUROSCI.0625-12.2012","article-title":"Rab8 modulates metabotropic glutamate receptor subtype 1 intracellular trafficking and signaling in a protein kinase C-dependent manner","volume":"32","author":"Esseltine","year":"2012","journal-title":"J. Neurosci."},{"key":"10.1016\/j.brainres.2025.149785_b0125","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/toxsci\/kfw196","article-title":"From the cover: manganese stimulates mitochondrial H2O2 production in SH-SY5Y human neuroblastoma cells over physiologic as well as toxicologic range","volume":"155","author":"Fernandes","year":"2017","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.brainres.2025.149785_b0130","first-page":"5080","article-title":"The PP1-R6 protein phosphatase holoenzyme is involved in the glucose-induced dephosphorylation and inactivation of AMP-activated protein kinase, a key regulator of insulin secretion, in MIN6 beta cells","volume":"24","author":"Garcia-Haro","year":"2010","journal-title":"FASEB J."},{"key":"10.1016\/j.brainres.2025.149785_b0135","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.nbd.2006.04.001","article-title":"Kinase activity is required for the toxic effects of mutant LRRK2\/dardarin","volume":"23","author":"Greggio","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.brainres.2025.149785_b0140","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S1474-4422(24)00121-2","article-title":"RAB32 Ser71Arg in autosomal dominant Parkinson\u2019s disease: linkage, association, and functional analyses","volume":"23","author":"Gustavsson","year":"2024","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.brainres.2025.149785_b0145","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1101\/gad.17420111","article-title":"AMP-activated protein kinase\u2014an energy sensor that regulates all aspects of cell function","volume":"25","author":"Hardie","year":"2011","journal-title":"Genes Dev."},{"key":"10.1016\/j.brainres.2025.149785_b0150","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2019.00654","article-title":"Manganese-induced neurotoxicity: new insights into the triad of protein misfolding, mitochondrial impairment, and neuroinflammation","volume":"13","author":"Harischandra","year":"2019","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.brainres.2025.149785_b0155","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.1242\/jcs.03275","article-title":"Characterization of the Rab8-specific membrane traffic route linked to protrusion formation","volume":"119","author":"Hattula","year":"2006","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.brainres.2025.149785_b0160","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1091\/mbc.E16-02-0091","article-title":"Rabin8 regulates neurite outgrowth in both GEF activity\u2013dependent and \u2013independent manners","volume":"27","author":"Homma","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.brainres.2025.149785_b0165","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.stem.2016.08.002","article-title":"Functional impairment in miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson\u2019s disease","volume":"19","author":"Hsieh","year":"2016","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.brainres.2025.149785_b0170","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1474-9726.2006.00202.x","article-title":"Calorie restriction mimetics: an emerging research field","volume":"5","author":"Ingram","year":"2006","journal-title":"Aging Cell"},{"key":"10.1016\/j.brainres.2025.149785_b0175","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-023-05964-0","article-title":"LRRK2 phosphorylation status and kinase activity regulate (macro)autophagy in a Rab8a\/Rab10-dependent manner","volume":"14","author":"Kania","year":"2023","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.brainres.2025.149785_b0180","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/cbin.10915","article-title":"Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism","volume":"42","author":"Ke","year":"2018","journal-title":"Cell Biol. Int."},{"key":"10.1016\/j.brainres.2025.149785_b0185","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adl3438","article-title":"LRRK2 regulates production of reactive oxygen species in cell and animal models of Parkinson\u2019s disease","volume":"16","author":"Keeney","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.brainres.2025.149785_b0190","article-title":"LRRK2 kinase plays a critical role in manganese-induced inflammation and apoptosis in microglia","volume":"14","author":"Kim","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.brainres.2025.149785_b0195","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.3390\/cells12212550","article-title":"LRRK2 attenuates antioxidant response in familial Parkinson\u2019s disease derived neural stem cells","volume":"12","author":"Kim","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.brainres.2025.149785_b0200","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.brainres.2025.149785_b0205","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1042\/BST20180462","article-title":"LRRK2 links genetic and sporadic Parkinson\u2019s disease","volume":"47","author":"Kluss","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.brainres.2025.149785_b0210","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1242\/bio.20148771","article-title":"Rab35 promotes the recruitment of Rab8, Rab13 and Rab36 to recycling endosomes through MICAL-L1 during neurite outgrowth","volume":"3","author":"Kobayashi","year":"2014","journal-title":"Biology Open"},{"key":"10.1016\/j.brainres.2025.149785_b0215","doi-asserted-by":"crossref","first-page":"7519","DOI":"10.3390\/ijerph120707519","article-title":"Manganese-induced parkinsonism and Parkinson\u2019s disease: shared and distinguishable features","volume":"12","author":"Kwakye","year":"2015","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"10.1016\/j.brainres.2025.149785_b0220","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1093\/hmg\/ddz201","article-title":"RAB8, RAB10 and RILPL1 contribute to both LRRK2 kinase\u2013mediated centrosomal cohesion and ciliogenesis deficits","volume":"28","author":"Lara Ord\u00f3nez","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.brainres.2025.149785_b0225","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1042\/BCJ20180589","article-title":"Kinase activity of mutant LRRK2 manifests differently in hetero-dimeric vs. homo-dimeric complexes","volume":"476","author":"Leandrou","year":"2019","journal-title":"Biochem. J"},{"key":"10.1016\/j.brainres.2025.149785_b0230","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.bbrc.2007.04.006","article-title":"The R1441C mutation of LRRK2 disrupts GTP hydrolysis","volume":"357","author":"Lewis","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.brainres.2025.149785_b0235","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/1873-3468.12555","article-title":"Rab8A regulates insulin-stimulated GLUT4 translocation in C2C12 myoblasts","volume":"591","author":"Li","year":"2017","journal-title":"FEBS Lett."},{"key":"10.1016\/j.brainres.2025.149785_b0240","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.neuron.2009.11.006","article-title":"Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson\u2019s disease-related mutant \u03b1-synuclein","volume":"64","author":"Lin","year":"2009","journal-title":"Neuron"},{"key":"10.1016\/j.brainres.2025.149785_b0245","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1042\/BJ20121772","article-title":"Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle","volume":"456","author":"Lobbestael","year":"2013","journal-title":"Biochem. J"},{"key":"10.1016\/j.brainres.2025.149785_b0250","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1021\/bi901726c","article-title":"Differential effects of divalent manganese and magnesium on the kinase activity of leucine-rich repeat kinase 2 (LRRK2)","volume":"49","author":"Lovitt","year":"2010","journal-title":"Biochemistry"},{"key":"10.1016\/j.brainres.2025.149785_b0255","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.brainres.2025.149785_b0260","doi-asserted-by":"crossref","first-page":"21386","DOI":"10.1074\/jbc.M113.528463","article-title":"Arsenite stress down-regulates phosphorylation and 14-3-3 binding of leucine-rich repeat kinase 2 (LRRK2), promoting self-association and cellular redistribution","volume":"289","author":"Mamais","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.brainres.2025.149785_b0265","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3001480","article-title":"Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia","volume":"19","author":"Mamais","year":"2021","journal-title":"PLoS Biol."},{"key":"10.1016\/j.brainres.2025.149785_b0270","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.stemcr.2024.01.001","article-title":"The LRRK2 kinase substrates RAB8a and RAB10 contribute complementary but distinct disease-relevant phenotypes in human neurons","volume":"19","author":"Mamais","year":"2024","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.brainres.2025.149785_b0275","doi-asserted-by":"crossref","unstructured":"Martinez Fiesco, J.A. et al. 14-3-3 binding maintains the Parkinson\u2019s associated kinase LRRK2 in an inactive state. bioRxiv 2024.11.22.624879 (2024) doi:10.1101\/2024.11.22.624879.","DOI":"10.1101\/2024.11.22.624879"},{"key":"10.1016\/j.brainres.2025.149785_b0280","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1002\/mds.28175","article-title":"Elevated in vitro kinase activity in peripheral blood mononuclear cells of leucine-rich repeat kinase 2 G2019S carriers: a novel enzyme-linked immunosorbent assay-based method","volume":"35","author":"Melachroinou","year":"2020","journal-title":"Mov. Disord."},{"key":"10.1016\/j.brainres.2025.149785_b0285","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.taap.2009.11.025","article-title":"Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats","volume":"243","author":"Minor","year":"2010","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.brainres.2025.149785_b0290","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1042\/BCJ20180248","article-title":"The Parkinson\u2019s disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human","volume":"475","author":"Mir","year":"2018","journal-title":"Biochem. J"},{"key":"10.1016\/j.brainres.2025.149785_b0295","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/j.1432-1033.1991.tb16172.x","article-title":"Evidence that AMP triggers phosphorylation as well as direct allosteric activation of rat liver AMP-activated protein kinase","volume":"199","author":"Moore","year":"1991","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.brainres.2025.149785_b0300","doi-asserted-by":"crossref","first-page":"3270","DOI":"10.1007\/s12035-021-02341-w","article-title":"Defective mitochondrial dynamics underlie manganese-induced neurotoxicity","volume":"58","author":"Morcillo","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.brainres.2025.149785_b0305","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1212\/WNL.0000000000001905","article-title":"UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2(G2019S) carriers and in vivo","volume":"85","author":"Mortiboys","year":"2015","journal-title":"Neurology"},{"key":"10.1016\/j.brainres.2025.149785_b0310","article-title":"Calorie restriction in humans: an update","author":"Most","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.brainres.2025.149785_b0315","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1042\/BJ20100483","article-title":"14-3-3 binding to LRRK2 is disrupted by multiple Parkinson\u2019s disease-associated mutations and regulates cytoplasmic localization","volume":"430","author":"Nichols","year":"2010","journal-title":"Biochem. J"},{"key":"10.1016\/j.brainres.2025.149785_b0320","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2022.105917","article-title":"LRRK2 protects immune cells against erastin-induced ferroptosis","volume":"175","author":"Oun","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.brainres.2025.149785_b0325","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.mito.2013.04.005","article-title":"Modifiers of the oligomycin sensitivity of the mitochondrial F1F0-ATPase","volume":"13","author":"Pagliarani","year":"2013","journal-title":"Mitochondrion"},{"key":"10.1016\/j.brainres.2025.149785_b0330","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2023.104879","article-title":"The role of microglial LRRK2 kinase in manganese-induced inflammatory neurotoxicity via NLRP3 inflammasome and RAB10-mediated autophagy dysfunction","volume":"299","author":"Pajarillo","year":"2023","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.brainres.2025.149785_b0335","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.1093\/hmg\/dds244","article-title":"G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization","volume":"21","author":"Papkovskaia","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.brainres.2025.149785_b0340","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1038\/s41467-023-38401-z","article-title":"Redefining the role of AMPK in autophagy and the energy stress response","volume":"14","author":"Park","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.brainres.2025.149785_b0345","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40360-016-0099-0","article-title":"Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies","volume":"17","author":"Peres","year":"2016","journal-title":"BMC Pharmacol. Toxicol."},{"key":"10.1016\/j.brainres.2025.149785_b0350","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/1873-3468.14492","article-title":"LRRK2 phosphorylation of Rab GTPases in Parkinson\u2019s disease","volume":"597","author":"Pfeffer","year":"2023","journal-title":"FEBS Lett."},{"key":"10.1016\/j.brainres.2025.149785_b0355","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.ajhg.2012.01.017","article-title":"Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease","volume":"90","author":"Quadri","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.brainres.2025.149785_b0360","doi-asserted-by":"crossref","unstructured":"Raig, N. D. et al. Type-II kinase inhibitors that target Parkinson\u2019s Disease-associated LRRK2. 2024.09.17.613365 Preprint at https:\/\/doi.org\/10.1101\/2024.09.17.613365 (2025).","DOI":"10.1126\/sciadv.adt2050"},{"key":"10.1016\/j.brainres.2025.149785_b0365","doi-asserted-by":"crossref","first-page":"32333","DOI":"10.1074\/jbc.M402096200","article-title":"Manganese induces the mitochondrial permeability transition in cultured astrocytes*","volume":"279","author":"Rao","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.brainres.2025.149785_b0370","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.cell.2013.03.044","article-title":"14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins","volume":"153","author":"Riou","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.brainres.2025.149785_b0375","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.1093\/hmg\/ddu138","article-title":"Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy","volume":"23","author":"Schapansky","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.brainres.2025.149785_b0380","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.brainres.2025.149785_b0385","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/s41467-021-21662-x","article-title":"Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking","volume":"12","author":"Schiweck","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.brainres.2025.149785_b0390","doi-asserted-by":"crossref","first-page":"14979","DOI":"10.1073\/pnas.1900289116","article-title":"The dynamic switch mechanism that leads to activation of LRRK2 is embedded in the DFG\u03c8 motif in the kinase domain","volume":"116","author":"Schmidt","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.brainres.2025.149785_b0395","doi-asserted-by":"crossref","first-page":"5181","DOI":"10.1091\/mbc.e09-06-0535","article-title":"MICAL-L1 links EHD1 to tubular recycling endosomes and regulates receptor recycling","volume":"20","author":"Sharma","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.brainres.2025.149785_b0400","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.bbrc.2016.10.126","article-title":"Redox dynamics of manganese as a mitochondrial life-death switch","volume":"482","author":"Smith","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.brainres.2025.149785_b0405","doi-asserted-by":"crossref","unstructured":"Steger, M., et al. Phosphoproteomics reveals that Parkinson\u2019s disease kinase LRRK2 regulates a subset of Rab GTPases. eLife 5, (2016).","DOI":"10.7554\/eLife.12813"},{"key":"10.1016\/j.brainres.2025.149785_b0410","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1042\/bj3450437","article-title":"The regulation of AMP-activated protein kinase by phosphorylation","volume":"345","author":"Stein","year":"2000","journal-title":"Biochem. J"},{"key":"10.1016\/j.brainres.2025.149785_b0415","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s11010-007-9575-6","article-title":"AICAR induces phosphorylation of AMPK in an ATM-dependent, LKB1-independent manner","volume":"306","author":"Sun","year":"2007","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.brainres.2025.149785_b0420","doi-asserted-by":"crossref","DOI":"10.1042\/BCJ20210375","article-title":"Impact of type II LRRK2 inhibitors on signalling and mitophagy","author":"Tasegian","year":"2021","journal-title":"Biochem. J."},{"key":"10.1016\/j.brainres.2025.149785_b0425","doi-asserted-by":"crossref","first-page":"14622","DOI":"10.1073\/pnas.0906334106","article-title":"R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice","volume":"106","author":"Tong","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.brainres.2025.149785_b0430","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41531-024-00683-5","article-title":"RedOx regulation of LRRK2 kinase activity by active site cysteines","volume":"10","author":"Trilling","year":"2024","journal-title":"Npj Parkinsons. Dis."},{"key":"10.1016\/j.brainres.2025.149785_b0435","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1074\/jbc.M116.766337","article-title":"Small GTPase Rab8a-recruited phosphatidylinositol 3-kinase \u03b3 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.brainres.2025.149785_b0440","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.258549","article-title":"Endosomal recycling tubule scission and integrin recycling involve the membrane curvature-supporting protein LITAF","volume":"134","author":"Wunderley","year":"2021","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.brainres.2025.149785_b0445","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.nbd.2012.05.020","article-title":"LRRK2 kinase activity mediates toxic interactions between genetic mutation and oxidative stress in a Drosophila model: suppression by curcumin","volume":"47","author":"Yang","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.brainres.2025.149785_b0450","article-title":"LRRK2 Gly2019Ser mutation promotes ER stress via interacting with THBS1\/TGF-\u03b21 in Parkinson\u2019s disease","volume":"10","author":"Yao","year":"2023","journal-title":"Adv. Sci. (weinh)"},{"key":"10.1016\/j.brainres.2025.149785_b0455","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1097\/JS9.0000000000002081","article-title":"Translational evaluation of metabolic risk factors impacting DBS efficacy for PD-related sleep and depressive disorders: preclinical, prospective and cohort studies","volume":"111","author":"Yao","year":"2025","journal-title":"Int. J. Surg."},{"key":"10.1016\/j.brainres.2025.149785_b0460","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1083\/jcb.200703047","article-title":"Functional dissection of Rab GTPases involved in primary cilium formation","volume":"178","author":"Yoshimura","year":"2007","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.brainres.2025.149785_b0465","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.nbd.2015.02.031","article-title":"Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice","volume":"78","author":"Yue","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.brainres.2025.149785_b0470","article-title":"LRRK2 regulates ferroptosis through the system Xc-GSH-GPX4 pathway in the neuroinflammatory mechanism of Parkinson\u2019s disease","volume":"239","author":"Z","year":"2024","journal-title":"J. Cell. Physiol."}],"container-title":["Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006899325003464?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006899325003464?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T09:18:15Z","timestamp":1779700695000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006899325003464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":94,"alternative-id":["S0006899325003464"],"URL":"https:\/\/doi.org\/10.1016\/j.brainres.2025.149785","relation":{},"ISSN":["0006-8993"],"issn-type":[{"value":"0006-8993","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Regulation of LRRK2 activity by metabolic stress and heavy metal exposure","name":"articletitle","label":"Article Title"},{"value":"Brain Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.brainres.2025.149785","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"149785"}}