{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:34:57Z","timestamp":1785429297212,"version":"3.56.0"},"reference-count":144,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology","doi-asserted-by":"publisher","award":["BT\/PR45527\/MED\/122\/322\/2022"],"award-info":[{"award-number":["BT\/PR45527\/MED\/122\/322\/2022"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BT\/PR45527\/MED\/122\/322\/2022"],"award-info":[{"award-number":["BT\/PR45527\/MED\/122\/322\/2022"]}],"id":[{"id":"https:\/\/ror.org\/03tjsyq23","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Parkinson\u2019s Disease & Movement Disorder Research Fund"},{"name":"UGC NET-JRF Ph.D."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although LRRK2 mutations modulate systemic glucose homeostasis and metabolic dysfunction precedes Parkinson\u2019s disease (PD) motor symptoms; the way in which pathogenic variants of LRRK2 disrupt astrocytic glucose metabolism and organellar homeostasis remains poorly understood. Here, we demonstrate that LRRK2-I1371V mutation causes profound metabolic and organellar dysfunction in LRRK2-I1371V PD-iPSC-derived astrocytes and U87 cells overexpressing I1371V variant. LRRK2-I1371V astrocytes exhibit significantly reduced GLUT1 expression and cell surface localization, resulting in impaired glucose uptake and decreased lactate production. This metabolic insufficiency correlates with cascading mitochondrial dysfunction, characterized by membrane depolarization, elevated reactive oxygen species, enhanced ubiquitination and reduced proteasomal activity. Reduced LAMP1\/LAMP2 expression, impaired lysosomal acidification, and selective cathepsin D deficiency were observed. Accumulation of undegraded cargo was confirmed by transmission electron microscopy upon \u03b1-synuclein exposure. ER stress was evident by upregulation of GADD34\/CHOP, increased phospho-PERK, and reduced nascent protein synthesis. Increased ER\u2013mitochondrial contact via MAMs and enhanced STIM1-ORAI3 clustering reflect compensatory but ultimately insufficient responses to energy stress. Our results reveal that LRRK2-I1371V induces glucose uptake deficits, leading to energy depletion and integrated ER\u2013mitochondria\u2013lysosome dysfunction, thus indicating restoration of astrocytic metabolic capacity as a potential therapeutic strategy for LRRK2-associated PD.<\/jats:p>","DOI":"10.3390\/ijms27083463","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"3463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LRRK2 I1371V Mutation Drives Astrocytic Glucose Metabolism Failure and Induces Integrated ER\u2013Mitochondria\u2013Lysosome Dysfunction in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Roon","family":"Banerjee","sequence":"first","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru 560029, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4964-438X","authenticated-orcid":false,"given":"Rashmi","family":"Santhoshkumar","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru 560029, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Holla","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru 560029, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7933-8826","authenticated-orcid":false,"given":"Nitish","family":"Kamble","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru 560029, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8016-9089","authenticated-orcid":false,"given":"Ravi","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru 560029, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod Kumar","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru 560029, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8864-473X","authenticated-orcid":false,"given":"Indrani","family":"Datta","sequence":"additional","affiliation":[{"name":"Department of Biophysics, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru 560029, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3934\/Neuroscience.2023017","article-title":"Depletion of dopamine in Parkinson\u2019s disease and relevant therapeutic options: A review of the literature","volume":"10","author":"Ramesh","year":"2023","journal-title":"AIMS Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.conb.2021.09.005","article-title":"PTEN-induced kinase 1 (PINK1) and Parkin: Unlocking a mitochondrial quality control pathway linked to Parkinson\u2019s disease","volume":"72","author":"Agarwal","year":"2022","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jeon, Y.-M., Kwon, Y., Jo, M., Lee, S., Kim, S., and Kim, H.-J. (2020). The role of glial mitochondria in \u03b1-synuclein toxicity. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.548283"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5171","DOI":"10.1007\/s00018-020-03584-x","article-title":"Glial cells in Parkinson\u2019s disease: Protective or deleterious?","volume":"77","author":"Domingues","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6455","DOI":"10.1111\/j.1742-4658.2009.07344.x","article-title":"LRRK2 in Parkinson\u2019s disease: Genetic and clinical studies from patients","volume":"276","author":"Kumari","year":"2009","journal-title":"FEBS J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"315\u2212322","DOI":"10.1002\/ana.20791","article-title":"Biochemical and pathological characterization of Lrrk2","volume":"59","author":"Giasson","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"388\u2212393","DOI":"10.1002\/ana.20731","article-title":"Lrrk2 and Lewy body disease","volume":"59","author":"Ross","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nguyen, A.P.T., Nguyen, L.T.N., Stokke, B.A., and Quinn, C.C. (2025). Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1569733"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"AN20090007","DOI":"10.1042\/AN20090007","article-title":"Leucine-rich repeat kinase 2 mutations and Parkinson\u2019s disease: Three questions","volume":"1","author":"Greggio","year":"2009","journal-title":"ASN Neuro"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jfma.2016.04.009","article-title":"Functional properties of LRRK2 mutations in Taiwanese Parkinson disease","volume":"116","author":"Chang","year":"2017","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"191","DOI":"10.5603\/PJNNS.a2022.0008","article-title":"LRRK2 R1441C mutation causing Parkinson\u2019s Disease in an Egyptian family","volume":"56","author":"Ali","year":"2022","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1212\/01.WNL.0000167552.79769.b3","article-title":"LRRK2 gene in Parkinson disease: Mutation analysis and case control association study","volume":"65","author":"Lang","year":"2005","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1002\/mds.21162","article-title":"Mutations in LRRK2 other than G2019S are rare in a North American\u2013 based sample of familial Parkinson\u2019s disease","volume":"21","author":"Pankratz","year":"2006","journal-title":"Mov. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1073\/pnas.0709098105","article-title":"Structure of the ROC domain from the Parkinson\u2019s disease-associated leucine rich repeat kinase 2 reveals a dimeric GTPase","volume":"105","author":"Deng","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s10048-009-0173-5","article-title":"A LRRK2 G2019S mutation carrier from Turkey shares the Japanese haplotype","volume":"10","author":"Pirkevi","year":"2009","journal-title":"Neurogenetics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/jhg.2011.79","article-title":"Comprehensive mutational analysis of LRRK2 reveals variants supporting association with autosomal dominant Parkinson\u2019s disease","volume":"56","author":"Seki","year":"2011","journal-title":"J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1155\/2012\/895065","article-title":"Evaluation of the role of LRRK2 gene in Parkinson\u2019s disease in an East Indian Cohort","volume":"32","author":"Sadhukhan","year":"2012","journal-title":"Dis. Markers"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jns.2015.04.002","article-title":"Identification of novel variants in LRRK2 gene in patients with Parkinson\u2019s disease in Serbian population","volume":"353","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101447","DOI":"10.1016\/j.scr.2019.101447","article-title":"Generation of induced pluripotent stem cells (IBMSi011-A) from a patient with Parkinson\u2019s disease carrying LRRK2 p.I1371V mutation","volume":"37","author":"Lin","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_20","first-page":"350","article-title":"Progression and treatment of a series of patients with advanced LRRK2-associated Parkinson\u2019s disease","volume":"38","author":"Sesar","year":"2023","journal-title":"Neurol. Engl. Ed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/mds.21281","article-title":"Neuropathology of Parkinson\u2019s disease associated with the LRRK2 Ile1371Val mutation","volume":"22","author":"Giordana","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.14802\/jmd.12009","article-title":"Genetics of Parkinson\u2019s disease-a clinical perspective","volume":"5","author":"Cheon","year":"2012","journal-title":"J. Mov. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1001\/jamaneurol.2014.2704","article-title":"Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease","volume":"72","author":"Kalia","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40035-022-00294-1","article-title":"Genetic heterogeneity on sleep disorders in Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"11","author":"Huang","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41531-023-00544-7","article-title":"Perspective on the current state of the LRRK2 field","volume":"9","author":"Taymans","year":"2023","journal-title":"Npj Park. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11910-015-0564-y","article-title":"LRRK2 pathways leading to neurodegeneration","volume":"15","author":"Cookson","year":"2015","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"167998","DOI":"10.1016\/j.jmb.2023.167998","article-title":"The role of LRRK2 in intracellular organelle dynamics","volume":"435","author":"Boecker","year":"2023","journal-title":"J. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/jnc.12949","article-title":"LRRK2 pathobiology in Parkinson\u2019s disease","volume":"131","author":"Martin","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/hmg\/ddr451","article-title":"Transcriptional responses to loss or gain of function of the leucine-rich repeat kinase 2 (LRRK2) gene uncover biological processes modulated by LRRK2 activity","volume":"21","author":"Nikonova","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xiong, Y., Coombes, C.E., Kilaru, A., Li, X., Gitler, A.D., Bowers, W.J., Dawson, V.L., Dawson, T.M., and Moore, D.J. (2010). GTPase activity plays a key role in the pathobiology of LRRK2. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1000902"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14474","DOI":"10.1038\/s41598-020-71329-8","article-title":"Metabolic alterations in Parkinson\u2019s disease astrocytes","volume":"10","author":"Sonninen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1097\/01.jnen.0000235121.98052.54","article-title":"LRRK2 expression in normal and pathologic human brain and in human cell lines","volume":"65","author":"Miklossy","year":"2006","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_33","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":"ref_34","doi-asserted-by":"crossref","unstructured":"Banerjee, R., Raj, A., Potdar, C., Pal, P.K., Yadav, R., Kamble, N., Holla, V., and Datta, I. (2023). Astrocytes Differentiated from LRRK2-I1371V Parkinson\u2019s-Disease-Induced Pluripotent Stem Cells Exhibit Similar Yield but Cell-Intrinsic Dysfunction in Glutamate Uptake and Metabolism, ATP Generation, and Nrf2-Mediated Glutathione Machinery. Cells, 12.","DOI":"10.3390\/cells12121592"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00401-022-02437-0","article-title":"Trafficking of the glutamate transporter is impaired in LRRK2-related Parkinson\u2019s disease","volume":"144","author":"Iovino","year":"2022","journal-title":"Acta Neuropathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4324","DOI":"10.3390\/cimb46050263","article-title":"Expression of G2019S LRRK2 in rat primary astrocytes mediates neurotoxicity and alters the dopamine synthesis pathway in N27 cells via astrocytic proinflammatory cytokines and neurotrophic factors","volume":"46","author":"Ho","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e5284","DOI":"10.1002\/nbm.5284","article-title":"Simultaneous assessment of cerebral glucose and oxygen metabolism and perfusion in rats using interleaved deuterium (2H) and oxygen-17 (17O) MRS","volume":"38","author":"Zhang","year":"2025","journal-title":"NMR Biomed."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Beard, E., Lengacher, S., Dias, S., Magistretti, P.J., and Finsterwald, C. (2022). Astrocytes as key regulators of brain energy metabolism: New therapeutic perspectives. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.825816"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1523\/JNEUROSCI.5430-07.2008","article-title":"Inhibition of monocarboxylate transporter 2 in the retrotrapezoid nucleus in rats: A test of the astrocyte\u2013neuron lactate-shuttle hypothesis","volume":"28","author":"Erlichman","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4196\/kjpp.24.388","article-title":"Brain energy homeostasis: The evolution of the astrocyte-neuron lactate shuttle hypothesis","volume":"29","author":"Kim","year":"2025","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40035-025-00467-8","article-title":"Parkinson\u2019s disease and glucose metabolism impairment","volume":"14","author":"Chen","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.neuron.2015.03.035","article-title":"A cellular perspective on brain energy metabolism and functional imaging","volume":"86","author":"Magistretti","year":"2015","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41531-023-00564-3","article-title":"Parkinson\u2019s disease neurons exhibit alterations in mitochondrial quality control proteins","volume":"9","author":"Chen","year":"2023","journal-title":"npj Park. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e3379","DOI":"10.6061\/clinics\/2021\/e3379","article-title":"Effect of metabolic syndrome on Parkinson\u2019s disease: A systematic review","volume":"76","author":"Souza","year":"2021","journal-title":"Clinics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.14336\/AD.2022.0325","article-title":"Association between Parkinson\u2019s disease and diabetes mellitus: From epidemiology, pathophysiology and prevention to treatment","volume":"13","author":"Yu","year":"2022","journal-title":"Aging Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1002\/2211-5463.13717","article-title":"LRRK2 negatively regulates glucose tolerance via regulation of membrane translocation of GLUT4 in adipocytes","volume":"13","author":"Kawakami","year":"2023","journal-title":"FEBS Open Bio"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1248\/bpb.b20-00377","article-title":"LRRK2 inhibition ameliorates dexamethasone-induced glucose intolerance via prevents impairment in GLUT4 membrane translocation in adipocytes","volume":"43","author":"Imai","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1038\/s41598-019-40808-y","article-title":"The Parkinson\u2019s disease-linked Leucine-rich repeat kinase 2 (LRRK2) is required for insulin-stimulated translocation of GLUT4","volume":"9","author":"Funk","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s00018-025-05810-w","article-title":"LRRK2 kinase modulates glucose-stimulated insulin secretion via RAB8 phosphorylation and ciliogenesis","volume":"82","author":"Dule","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1089\/scd.2023.0283","article-title":"Impaired Sonic Hedgehog Responsiveness of Induced Pluripotent Stem Cell-Derived Floor Plate Cells Carrying the LRRK2-I1371V Mutation Contributes to the Ontogenic Origin of Lower Dopaminergic Neuron Yield","volume":"33","author":"Potdar","year":"2024","journal-title":"Stem Cells Dev."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Singh, K., Banerjee, R., Potdar, C., Shaw, A., Rakshith, R., Kamble, N., Holla, V., Yadav, R., Pal, P.K., and Datta, I. (2026). Membrane Dysfunction as a Central Mechanism in LRRK2-Associated Parkinson\u2019s Disease: Comparative Analysis of G2019S and I1371V Mutations. Cells, 15.","DOI":"10.20944\/preprints202601.0493.v1"},{"key":"ref_52","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":"ref_53","doi-asserted-by":"crossref","first-page":"e100875","DOI":"10.15252\/embj.2018100875","article-title":"LRRK 2 regulates endoplasmic reticulum\u2013mitochondrial tethering through the PERK-mediated ubiquitination pathway","volume":"39","author":"Toyofuku","year":"2020","journal-title":"EMBO J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/15548627.2019.1603548","article-title":"LRRK2 mutations impair depolarization-induced mitophagy through inhibition of mitochondrial accumulation of RAB10","volume":"16","author":"Wauters","year":"2020","journal-title":"Autophagy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1093\/hmg\/ddz004","article-title":"LRRK2 impairs PINK1\/Parkin-dependent mitophagy via its kinase activity: Pathologic insights into Parkinson\u2019s disease","volume":"28","author":"Bonello","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.1093\/hmg\/ddz126","article-title":"Mitochondrial clearance and maturation of autophagosomes are compromised in LRRK2 G2019S familial Parkinson\u2019s disease patient fibroblasts","volume":"28","author":"Korecka","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.stemcr.2019.03.004","article-title":"Neural stem cells of Parkinson\u2019s disease patients exhibit aberrant mitochondrial morphology and functionality","volume":"12","author":"Walter","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Chen, M.-M., Li, Y., Deng, S.-L., Zhao, Y., Lian, Z.-X., and Yu, K. (2022). Mitochondrial function and reactive oxygen\/nitrogen species in skeletal muscle. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.826981"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1093\/hmg\/ddad102","article-title":"Mitochondrial dysfunction and mitophagy defects in LRRK2-R1441C Parkinson\u2019s disease models","volume":"32","author":"Williamson","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00018-015-2052-6","article-title":"The endoplasmic reticulum: Structure, function and response to cellular signaling","volume":"73","author":"Schwarz","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Costa, C.A., Manaa, W.E., Duplan, E., and Checler, F. (2020). The endoplasmic reticulum stress\/unfolded protein response and their contributions to Parkinson\u2019s disease physiopathology. Cells, 9.","DOI":"10.3390\/cells9112495"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.toxlet.2020.01.019","article-title":"Endoplasmic reticulum stress, an important factor in the development of Parkinson\u2019s disease","volume":"324","author":"Mou","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.semcdb.2007.09.003","article-title":"The endoplasmic reticulum and the unfolded protein response","volume":"Volume 18","author":"Malhotra","year":"2007","journal-title":"Seminars in Cell & Developmental Biology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.bbamcr.2008.10.016","article-title":"Sorting of lysosomal proteins","volume":"1793","author":"Braulke","year":"2009","journal-title":"Biochim. et Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrm2745","article-title":"Lysosome biogenesis and lysosomal membrane proteins: Trafficking meets function","volume":"10","author":"Saftig","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/mds.25462","article-title":"Lysosomal impairment in Parkinson\u2019s disease","volume":"28","author":"Dehay","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Inpanathan, S., and Botelho, R.J. (2019). The lysosome signaling platform: Adapting with the times. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00113"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Todkar, K., Ilamathi, H.S., and Germain, M. (2017). Mitochondria and lysosomes: Discovering bonds. Front. Cell Dev. Biol., 5.","DOI":"10.3389\/fcell.2017.00106"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41420-023-01353-w","article-title":"Synergistic mechanism between the endoplasmic reticulum and mitochondria and their crosstalk with other organelles","volume":"9","author":"Zhang","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102453","DOI":"10.1016\/j.ceca.2021.102453","article-title":"Ca2+ handling at the mitochondria-ER contact sites in neurodegeneration","volume":"98","author":"Lim","year":"2021","journal-title":"Cell Calcium"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41392-023-01503-7","article-title":"The mitophagy pathway and its implications in human diseases","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_72","first-page":"158544","article-title":"ER morphology and endo-lysosomal crosstalk: Functions and disease implications","volume":"1865","author":"Lee","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1002\/mds.23148","article-title":"A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson\u2019s disease","volume":"25","author":"Snow","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.tins.2021.12.004","article-title":"ysosomal dysfunction in neurodegeneration: Emerging concepts and methods","volume":"45","author":"Udayar","year":"2022","journal-title":"Trends Neurosci."},{"key":"ref_75","unstructured":"Rissardo, J.P., and Caprara, A.F. (2025). Disease Modifying Therapies for Parkinson\u2019s Disease: Biological Mechanisms, Pharmacological Strategies, and Clinical Pipeline. Preprints, 2025122271."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.parkreldis.2015.05.022","article-title":"Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson\u2019s disease","volume":"21","author":"Yoritaka","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1001\/jama.2015.120","article-title":"Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: A randomized clinical trial","volume":"313","author":"Kieburtz","year":"2015","journal-title":"Jama"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S1474-4422(23)00455-6","article-title":"Venglustat in GBA1-related Parkinson\u2019s disease","volume":"23","author":"Zimran","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"a008763","DOI":"10.1101\/cshperspect.a008763","article-title":"Metabolic stress in autophagy and cell death pathways","volume":"4","author":"Altman","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/humu.21582","article-title":"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death","volume":"32","author":"Angeles","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40478-019-0716-4","article-title":"Parkinson\u2019s disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes","volume":"7","author":"Lee","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2303711","DOI":"10.1002\/advs.202303711","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."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.stemcr.2018.12.011","article-title":"Patient-specific iPSC-derived astrocytes contribute to non-cell-autonomous neurodegeneration in Parkinson\u2019s disease","volume":"12","author":"Carola","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, C.-A., Rodrigues, L., Bobermin, L.D., Zanotto, C., Vizuete, A., Quincozes-Santos, A., Souza, D.O., and Leite, M.C. (2019). Glycolysis-derived compounds from astrocytes that modulate synaptic communication. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.01035"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/j.bbagen.2014.02.015","article-title":"LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model","volume":"1840","author":"Pereira","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"13807","DOI":"10.1073\/pnas.96.24.13807","article-title":"Regulation of mitochondrial ATP synthesis by calcium: Evidence for a long-term metabolic priming","volume":"96","author":"Jouaville","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s11011-025-01697-5","article-title":"Targeting glucose transporters in parkinson\u2019s disease: A novel metabolic approach for disease modification","volume":"40","author":"Singh","year":"2025","journal-title":"Metab. Brain Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e12813","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":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BCJ20170802","article-title":"Development of phospho-specific Rab protein antibodies to monitor in vivo activity of the LRRK2 Parkinson\u2019s disease kinase","volume":"475","author":"Lis","year":"2018","journal-title":"Biochem. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4738","DOI":"10.1074\/jbc.RA118.005008","article-title":"The G2019S variant of leucine-rich repeat kinase 2 (LRRK2) alters endolysosomal trafficking by impairing the function of the GTPase RAB8A","volume":"294","author":"Thomas","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41531-022-00334-7","article-title":"\u03b1-Synuclein induced cholesterol lowering increases tonic and reduces depolarization-evoked synaptic vesicle recycling and glutamate release","volume":"8","author":"Lazarevic","year":"2022","journal-title":"npj Park. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.neuropharm.2018.01.039","article-title":"Membrane cholesterol removal and replenishment affect rat and monkey brain monoamine transporters","volume":"133","author":"Morissette","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e40202","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":"ref_94","first-page":"719","article-title":"Alterations in mitochondrial membrane potential in peripheral blood mononuclear cells in Parkinson\u2019s Disease: Potential for a novel biomarker","volume":"36","author":"Qadri","year":"2018","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1093\/hmg\/ddx320","article-title":"LRRK2 G2019S-induced mitochondrial DNA damage is LRRK2 kinase dependent and inhibition restores mtDNA integrity in Parkinson\u2019s disease","volume":"26","author":"Howlett","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"141ra90","DOI":"10.1126\/scitranslmed.3003985","article-title":"Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson\u2019s disease","volume":"4","author":"Cooper","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.nbd.2013.10.013","article-title":"LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson\u2019s disease patients: Reversal by gene correction","volume":"62","author":"Sanders","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1089\/scd.2013.0163","article-title":"The Parkinson\u2019s disease-associated LRRK2 mutation R1441G inhibits neuronal differentiation of neural stem cells","volume":"22","author":"Bahnassawy","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jchemneu.2018.02.001","article-title":"Nimodipine attenuates the parkinsonian neurotoxin, MPTP-induced changes in the calcium binding proteins, calpain and calbindin","volume":"95","author":"Singh","year":"2019","journal-title":"J. Chem. Neuroanat."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1093\/hmg\/dds003","article-title":"LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1","volume":"21","author":"Wang","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/j.freeradbiomed.2011.06.033","article-title":"Cross talk between mitochondria and NADPH oxidases","volume":"51","author":"Dikalov","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Ge, T., Yang, J., Zhou, S., Wang, Y., Li, Y., and Tong, X. (2020). The role of the pentose phosphate pathway in diabetes and cancer. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00365"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"eaav0725","DOI":"10.1126\/science.aav0725","article-title":"Substrate-engaged 26 S proteasome structures reveal mechanisms for ATP-hydrolysis\u2013driven translocation","volume":"362","author":"Goodall","year":"2018","journal-title":"Science"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1756-6606-2-5","article-title":"Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo","volume":"2","author":"Cullen","year":"2009","journal-title":"Mol. Brain"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1756-6606-1-17","article-title":"Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity","volume":"1","author":"Qiao","year":"2008","journal-title":"Mol. Brain"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Chiu, C.-C., Chen, Y.-L., Weng, Y.-H., Liu, S.-Y., Li, H.-L., Yeh, T.-H., and Wang, H.-L. (2024). Downregulation of Protease Cathepsin D and Upregulation of Pathologic \u03b1-Synuclein Mediate Paucity of DNAJC6-Induced Degeneration of Dopaminergic Neurons. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126711"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1093\/brain\/awl107","article-title":"Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis","volume":"129","author":"Siintola","year":"2006","journal-title":"Brain"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1097\/NEN.0b013e318238fc28","article-title":"Morphologic and functional correlates of synaptic pathology in the cathepsin D knockout mouse model of congenital neuronal ceroid lipofuscinosis","volume":"70","author":"Koch","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neulet.2019.04.003","article-title":"Autophagy dysfunction in peripheral blood mononuclear cells of Parkinson\u2019s disease patients","volume":"704","author":"Papagiannakis","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"104620","DOI":"10.1016\/j.nbd.2019.104620","article-title":"Glucocerebrosidase activity, cathepsin D and monomeric \u03b1-synuclein interactions in a stem cell derived neuronal model of a PD associated GBA1 mutation","volume":"134","author":"Yang","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Barrett, A.J. (1980). Cathepsin D: The lysosomal aspartic proteinase. Protein Degradation in Health and Disease, John Wiley & Sons.","DOI":"10.1002\/9780470720585.ch3"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"183341","DOI":"10.1016\/j.bbamem.2020.183341","article-title":"Regulation and function of V-ATPases in physiology and disease","volume":"1862","author":"Collins","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_113","first-page":"25","article-title":"Modulating lysosomal pH: A molecular and nanoscale materials design perspective","volume":"2","author":"Zeng","year":"2020","journal-title":"J. Life Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev-physiol-012110-142317","article-title":"Lysosomal acidification mechanisms","volume":"74","author":"Mindell","year":"2012","journal-title":"Annu. Rev. Physiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1186\/s12964-024-01928-9","article-title":"Dysregulation of protein degradation and alteration of secretome in \u03b1-synuclein-exposed astrocytes: Implications for dopaminergic neuronal dysfunction","volume":"22","author":"Raj","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Lee, S.-J., Desplats, P., Lee, H.-J., Spencer, B., and Masliah, E. (2012). Cell-to-cell transmission of \u03b1-synuclein aggregates. Amyloid Proteins: Methods and Protocols, Humana Press.","DOI":"10.1007\/978-1-61779-551-0_23"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"11835","DOI":"10.1523\/JNEUROSCI.0983-17.2017","article-title":"Human astrocytes transfer aggregated alpha-synuclein via tunneling nanotubes","volume":"37","author":"Rostami","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/emboj.2012.32","article-title":"A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB","volume":"31","author":"Settembre","year":"2012","journal-title":"EMBO J."},{"key":"ref_119","first-page":"ra42","article-title":"The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis","volume":"5","author":"Petit","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13395-021-00280-7","article-title":"The SarcoEndoplasmic Reticulum Calcium ATPase (SERCA) pump: A potential target for intervention in aging and skeletal muscle pathologies","volume":"11","author":"Xu","year":"2021","journal-title":"Skelet. Muscle"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nrm3412","article-title":"Mitochondria as sensors and regulators of calcium signalling","volume":"13","author":"Rizzuto","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41580-018-0052-8","article-title":"The machineries, regulation and cellular functions of mitochondrial calcium","volume":"19","author":"Giorgi","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.2337\/db18-1112","article-title":"Differential effect of glucose on ER-mitochondria Ca2+ exchange participates in insulin secretion and glucotoxicity-mediated dysfunction of \u03b2-cells","volume":"68","author":"Dingreville","year":"2019","journal-title":"Diabetes"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4749","DOI":"10.1038\/s41380-025-03069-y","article-title":"Glucose restriction induces degeneration of neurons with mitochondrial DNA depletion by altering ER-mitochondria calcium transfer","volume":"3","author":"Zhou","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_125","first-page":"29","article-title":"ER stress and the unfolded protein response","volume":"569","author":"Kaufman","year":"2005","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/332462a0","article-title":"The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins","volume":"332","author":"Kozutsumi","year":"1988","journal-title":"Nature"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.neuron.2017.09.056","article-title":"Cell biology of astrocyte-synapse interactions","volume":"96","author":"Allen","year":"2017","journal-title":"Neuron"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.3727\/096368911X600948","article-title":"CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice","volume":"21","author":"Airavaara","year":"2012","journal-title":"Cell Transplant."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4912","DOI":"10.1046\/j.1432-1327.2000.01597.x","article-title":"Glutathione metabolism in brain: Metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species","volume":"267","author":"Dringen","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.freeradbiomed.2009.05.004","article-title":"Mitochondria and reactive oxygen species","volume":"47","author":"Kowaltowski","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Norwitz, N.G., Hu, M.T., and Clarke, K. (2019). The mechanisms by which the ketone body D-\u03b2-hydroxybutyrate may improve the multiple cellular pathologies of Parkinson\u2019s disease. Front. Nutr., 6.","DOI":"10.3389\/fnut.2019.00063"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S1474-4422(21)00377-X","article-title":"Cholinergic system changes in Parkinson\u2019s disease: Emerging therapeutic approaches","volume":"21","author":"Yarnall","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1212\/01.WNL.0000152046.11390.45","article-title":"Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study","volume":"64","author":"VanItallie","year":"2005","journal-title":"Neurology"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s12031-010-9336-y","article-title":"Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity","volume":"42","author":"Yang","year":"2010","journal-title":"J. Mol. Neurosci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1007\/s12035-015-9672-6","article-title":"Glucose transporters at the blood-brain barrier: Function, regulation and gateways for drug delivery","volume":"54","author":"Patching","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Dzamko, N.L. (2017). LRRK2 and the immune system. Leucine-Rich Repeat Kinase 2 (LRRK2), Springer.","DOI":"10.1007\/978-3-319-49969-7_7"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41582-019-0301-2","article-title":"LRRK2 in Parkinson disease: Challenges of clinical trials","volume":"16","author":"Tolosa","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cger.2019.08.002","article-title":"Parkinson disease epidemiology, pathology, genetics, and pathophysiology","volume":"36","author":"Simon","year":"2020","journal-title":"Clin. Geriatr. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"Global, regional, and national burden of neurological disorders, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Feigin","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/jnr.24994","article-title":"Impact of monomeric and aggregated wild-type and A30P\/A53T double-mutant \u03b1-synuclein on antioxidant mechanism and glutamate metabolic profile of cultured astrocytes","volume":"100","author":"Raj","year":"2022","journal-title":"J. Neurosci. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1002\/jcb.25570","article-title":"Influence of 6-Hydroxydopamine Toxicity on \u03b1-Synuclein Phosphorylation, Resting Vesicle Expression, and Vesicular Dopamine Release","volume":"117","author":"Ganapathy","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5309","DOI":"10.1007\/s12035-023-03400-0","article-title":"Presence of extracellular alpha-synuclein aggregates trigger astrocytic degeneration through enhanced membrane rigidity and deregulation of store-operated calcium entry (SOCE) into the endoplasmic reticulum","volume":"60","author":"Raj","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1089\/scd.2020.0018","article-title":"Evaluating in vitro neonatal hypoxic-ischemic injury using neural progenitors derived from human embryonic stem cells","volume":"29","author":"Sowmithra","year":"2020","journal-title":"Stem Cells Dev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1007\/s12031-020-01777-4","article-title":"A dominant C150Y mutation in FHL1 induces structural alterations in LIM2 domain causing protein aggregation in human and Drosophila indirect flight muscles","volume":"71","author":"Santhoshkumar","year":"2021","journal-title":"J. Mol. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T12:06:09Z","timestamp":1776945969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":144,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083463"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083463","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,12]]}}}