{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:15:33Z","timestamp":1788250533783,"version":"build-2803163510"},"reference-count":167,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de S\u00e3o Paulo","award":["2024\/07829-5"],"award-info":[{"award-number":["2024\/07829-5"]}]},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de S\u00e3o Paulo","award":["2024\/17577-3"],"award-info":[{"award-number":["2024\/17577-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder in which metabolic, inflammatory and proteostatic disturbances converge to drive dopaminergic neuron loss and widespread network failure. In this narrative review, we synthesize clinical, epidemiological and experimental evidence to organize PD pathophysiology around three interconnected metabolic axes: mitochondrial dysfunction and impaired glucose and lipid metabolism; chronic oxidative stress; and glial reprogramming and neuroinflammation, with \u03b1-synuclein acting as a central integrator at their interface. We then map how currently available dopaminergic, neuromodulatory and rehabilitative therapies interact with these axes, largely providing downstream symptomatic compensation while leaving core metabolic and inflammatory drivers only partially addressed. Next, we review RNA sequencing (RNA-Seq) and related transcriptomic studies in human brain and peripheral tissues, highlighting convergent differentially expressed genes in mitochondrial, synaptic, immune and proteostasis pathways, as well as major methodological challenges and opportunities for molecular subtyping and biomarker discovery. Together, these lines of evidence support a systems-level view of PD in which \u03b1-synuclein\u2013centered metabolic failure and glial dysregulation are key therapeutic targets and in which high-quality RNA-Seq, integrated with advanced bioinformatics, may help define biologically grounded PD endotypes and accelerate the development of truly disease-modifying interventions.<\/jats:p>","DOI":"10.3390\/cimb48030254","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:58:03Z","timestamp":1772114283000},"page":"254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Parkinson\u2019s Disease: From Metabolism to Genetics\u2014A Comprehensive Review"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8119-0078","authenticated-orcid":false,"given":"Cauan","family":"Duarte","sequence":"first","affiliation":[{"name":"Post-Graduation Program in Endocrinology and Metabolism, Paulista School of Medicine, Federal University of S\u00e3o Paulo (EPM-UNIFESP), S\u00e3o Paulo 04021-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edislane Barreiros de","family":"Souza","sequence":"additional","affiliation":[{"name":"Faculty of Science and Letters, S\u00e3o Paulo State University (UNESP), Assis Campus, Assis 01049-010, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Rafael","family":"Dias-Pinto","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Endocrinology and Metabolism, Paulista School of Medicine, Federal University of S\u00e3o Paulo (EPM-UNIFESP), S\u00e3o Paulo 04021-001, Brazil"},{"name":"BioDecision Analytics, S\u00e3o Paulo 01451-917, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-2577","authenticated-orcid":false,"given":"Rodrigo Pinheiro","family":"Araldi","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Endocrinology and Metabolism, Paulista School of Medicine, Federal University of S\u00e3o Paulo (EPM-UNIFESP), S\u00e3o Paulo 04021-001, Brazil"},{"name":"BioDecision Analytics, S\u00e3o Paulo 01451-917, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1176\/jnp.14.2.223","article-title":"An Essay on the Shaking Palsy","volume":"14","author":"Parkinson","year":"2002","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/ana.410380304","article-title":"Aging, Energy, and Oxidative Stress in Neurodegenerative Diseases","volume":"38","author":"Beal","year":"1995","journal-title":"Ann. Neurol."},{"key":"ref_3","first-page":"147","article-title":"Insulin, IGF-1 and Longevity","volume":"1","year":"2010","journal-title":"Aging Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.arr.2017.12.007","article-title":"The Genetics of Parkinson Disease","volume":"42","author":"Deng","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_5","unstructured":"Stoker, T.B., and Greenland, J.C. (2018). Parkinson\u2019s Disease: Etiology, Neuropathology, and Pathogenesis. Parkinson\u2019s Disease: Pathogenesis and Clinical Aspects, Codon Publications."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Araldi, R.P., D\u2019Amelio, F., Vigerelli, H., De Melo, T.C., and Kerkis, I. (2020). Stem Cell-Derived Exosomes as Therapeutic Approach for Neurodegenerative Disorders: From Biology to Biotechnology. Cells, 9.","DOI":"10.3390\/cells9122663"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Basile, M.S., Battaglia, G., Bruno, V., Mangano, K., Fagone, P., Petralia, M.C., Nicoletti, F., and Cavalli, E. (2020). The Dichotomic Role of Macrophage Migration Inhibitory Factor in Neurodegeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21083023"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e080952","DOI":"10.1136\/bmj-2024-080952","article-title":"Projections for Prevalence of Parkinson\u2019s Disease and Its Driving Factors in 195 Countries and Territories to 2050: Modelling Study of Global Burden of Disease Study 2021","volume":"388","author":"Su","year":"2025","journal-title":"BMJ"},{"key":"ref_9","first-page":"S3","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Park. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1177\/0898264313514443","article-title":"Mortality from Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Dementias in France and Italy: A Comparison Using the Multiple Cause-of-Death Approach","volume":"26","author":"Demuru","year":"2014","journal-title":"J. Aging Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"331","DOI":"10.4322\/2526-8910.ctoao1229","article-title":"Doen\u00e7a de Parkinson: O Tratamento Terap\u00eautico Ocupacional Na Perspectiva Dos Profissionais e Dos Idosos","volume":"27","author":"Silva","year":"2019","journal-title":"Cad. Bras. Ter. Ocup."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/mds.29682","article-title":"Prevalence and Incidence of Parkinson\u2019s Disease in Latin America: A Meta-Analysis","volume":"39","author":"Kim","year":"2024","journal-title":"Mov. Disord."},{"key":"ref_13","first-page":"101046","article-title":"Prevalence, Distribution and Future Projections of Parkinson Disease in Brazil: Insights from the ELSI-Brazil Cohort Study","volume":"44","author":"Schlickmann","year":"2025","journal-title":"Lancet Reg. Health Am."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"321","DOI":"10.36557\/2674-8169.2024v6n9p321-332","article-title":"Descri\u00e7\u00e3o Do Perfil Epidemiol\u00f3gico Por Doen\u00e7a de Parkinson Entre 2021 e 2023","volume":"6","year":"2024","journal-title":"Braz. J. Implantol. Health Sci."},{"key":"ref_15","unstructured":"GBD 2016 Parkinson\u2019s Disease Collaborators (2018). Global, Regional, and National Burden of Parkinson\u2019s Disease, 1990\u20132016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 17, 939\u2013953."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105897","DOI":"10.1016\/j.parkreldis.2023.105897","article-title":"Average Annual Cost of Parkinson\u2019s Disease in a Brazilian Multiethnic Population","volume":"117","author":"Bovolenta","year":"2023","journal-title":"Park. Relat. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S1474-4422(24)00038-3","article-title":"Global, Regional, and National Burden of Disorders Affecting the Nervous System, 1990\u20132021: A Systematic Analysis for the Global Burden of Disease Study 2021","volume":"23","author":"Steinmetz","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1002\/mds.29995","article-title":"Systematic Review of the Cost of Illness of Parkinson\u2019s Disease from a Societal Perspective","volume":"39","author":"Wijers","year":"2024","journal-title":"Mov. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.neuron.2019.01.038","article-title":"Spatial and Temporal Locomotor Learning in Mouse Cerebellum","volume":"102","author":"Darmohray","year":"2019","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"602\u2013602.e1","DOI":"10.1016\/j.cell.2020.01.017","article-title":"SnapShot: Lysosomal Storage Diseases","volume":"180","author":"Martina","year":"2020","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neurobiolaging.2020.03.002","article-title":"Amyloid-Beta Burden Predicts Prospective Decline in Body Mass Index in Clinically Normal Adults","volume":"93","author":"Rabin","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Patil, P., and Ford, W.R. (2024). Parkinson\u2019s Disease Recognition Using Decorrelated Convolutional Neural Networks: Addressing Imbalance and Scanner Bias in Rs-fMRI Data. Biosensors, 14.","DOI":"10.20944\/preprints202403.1349.v1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"165757","DOI":"10.1016\/j.bbadis.2020.165757","article-title":"Genome-Wide Screening of Functional Long Noncoding RNAs in the Epicardial Adipose Tissues of Atrial Fibrillation","volume":"1866","author":"Shi","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.neuro.2020.03.005","article-title":"Analysis of Behavioral Changes in Zebrafish (Danio Rerio) Larvae Caused by Aminoglycoside-Induced Damage to the Lateral Line and Muscles","volume":"78","author":"Han","year":"2020","journal-title":"NeuroToxicology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.bbi.2020.03.003","article-title":"Fentanyl Self-Administration Impacts Brain Immune Responses in Male Sprague-Dawley Rats","volume":"87","author":"Ezeomah","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Deng, Y., Huang, X., Hu, Y., Zhong, W., Zhang, H., Mo, C., Wang, H., Ding, B.-S., and Wang, C. (2023). Deficiency of Endothelial FGFR1 Signaling via Upregulation of ROCK2 Activity Aggravated ALI\/ARDS. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1041533"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.3390\/cimb46030130","article-title":"Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases","volume":"46","author":"Bartman","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9089","DOI":"10.1074\/jbc.M710012200","article-title":"Mitochondrial Import and Accumulation of Alpha-Synuclein Impair Complex I in Human Dopaminergic Neuronal Cultures and Parkinson Disease Brain","volume":"283","author":"Devi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1074\/jbc.M310341200","article-title":"Characterization of Superoxide-Producing Sites in Isolated Brain Mitochondria","volume":"279","author":"Kudin","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1023\/B:NERE.0000014827.94562.4b","article-title":"Initiation of Neuronal Damage by Complex I Deficiency and Oxidative Stress in Parkinson\u2019s Disease","volume":"29","author":"Tretter","year":"2004","journal-title":"Neurochem. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nelson, D.L., and Cox, M.M. (2001). Lehninger Biochemie, Springer.","DOI":"10.1007\/978-3-662-08289-8"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7023","DOI":"10.1113\/JP273839","article-title":"Oxidative Phosphorylation: Regulation and Role in Cellular and Tissue Metabolism","volume":"595","author":"Wilson","year":"2017","journal-title":"J. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s12276-022-00802-3","article-title":"Tracing the Lactate Shuttle to the Mitochondrial Reticulum","volume":"54","author":"Brooks","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.arr.2004.05.001","article-title":"Cognitive Reserve and the Neurobiology of Cognitive Aging","volume":"3","author":"Whalley","year":"2004","journal-title":"Ageing Res. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12964-025-02308-7","article-title":"Mitochondrial Dysfunction in the Regulation of Aging and Aging-Related Diseases","volume":"23","author":"Zhang","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_36","first-page":"2495","article-title":"Mitochondrial Dysfunction in Aging and Age-Related Disorders","volume":"16","author":"Adlimoghaddam","year":"2025","journal-title":"Aging Dis."},{"key":"ref_37","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_38","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_39","doi-asserted-by":"crossref","unstructured":"Szablewski, L. (2025). Human Glucose Transporters in Health and Selected Neurodegenerative Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157392"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s00702-024-02863-2","article-title":"Mitochondrial Dysfunction in Parkinson\u2019s Disease","volume":"131","author":"Hattori","year":"2024","journal-title":"J. Neural Transm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13024-023-00676-7","article-title":"Mitochondrial Dysfunction in Parkinson\u2019s Disease\u2014A Key Disease Hallmark with Therapeutic Potential","volume":"18","author":"Henrich","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Fl\u00f8nes, I.H., and Tzoulis, C. (2022). Mitochondrial Respiratory Chain Dysfunction\u2014A Hallmark Pathology of Idiopathic Parkinson\u2019s Disease?. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.874596"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s11064-025-04559-9","article-title":"The Mitochondrial-Astrocyte-Neuron Triad Hypothesis in Parkinson\u2019s Disease: A Toxic Feedback Loop of Metabolism, Aggregation, and Oxidative Stress","volume":"50","author":"Walecha","year":"2025","journal-title":"Neurochem. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ostrakhovitch, E.A., Ono, K., and Yamasaki, T.R. (2025). Metabolomics in Parkinson\u2019s Disease and Correlation with Disease State. Metabolites, 15.","DOI":"10.3390\/metabo15030208"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Mason, S. (2017). Lactate Shuttles in Neuroenergetics\u2014Homeostasis, Allostasis and Beyond. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00043"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.cmet.2011.08.016","article-title":"Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation","volume":"14","author":"Allaman","year":"2011","journal-title":"Cell Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1042\/BST20170501","article-title":"Mitochondrial Abnormalities in Parkinson\u2019s Disease and Alzheimer\u2019s Disease: Can Mitochondria Be Targeted Therapeutically?","volume":"46","author":"Macdonald","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature10324","article-title":"\u03b1-Synuclein Occurs Physiologically as a Helically Folded Tetramer That Resists Aggregation","volume":"477","author":"Bartels","year":"2011","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41531-024-00842-8","article-title":"Mitochondrial Oxidant Stress Promotes \u03b1-Synuclein Aggregation and Spreading in Mice with Mutated Glucocerebrosidase","volume":"10","author":"Rollar","year":"2024","journal-title":"npj Park. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/j.1471-4159.1990.tb02325.x","article-title":"Mitochondrial Complex I Deficiency in Parkinson\u2019s Disease","volume":"54","author":"Schapira","year":"1990","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s Disease","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"\u03b1-Synuclein in Lewy Bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e41981","DOI":"10.1016\/j.heliyon.2025.e41981","article-title":"Alpha Synuclein and Inflammaging","volume":"11","author":"Putnam","year":"2025","journal-title":"Heliyon"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4578462","DOI":"10.1155\/2019\/4578462","article-title":"Current Progress of Mitochondrial Quality Control Pathways Underlying the Pathogenesis of Parkinson\u2019s Disease","volume":"2019","author":"Jiang","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"101263","DOI":"10.1016\/j.arr.2021.101263","article-title":"Oxidative Stress and Regulated Cell Death in Parkinson\u2019s Disease","volume":"67","author":"Amaral","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_56","first-page":"9163040","article-title":"The Sources of Reactive Oxygen Species and Its Possible Role in the Pathogenesis of Parkinson\u2019s Disease","volume":"2018","author":"Weng","year":"2018","journal-title":"Park. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41540-020-00150-w","article-title":"ROS Networks: Designs, Aging, Parkinson\u2019s Disease and Precision Therapies","volume":"6","author":"Sharma","year":"2020","journal-title":"npj Syst. Biol. Appl."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gogna, T., Housden, B.E., and Houldsworth, A. (2024). Exploring the Role of Reactive Oxygen Species in the Pathogenesis and Pathophysiology of Alzheimer\u2019s and Parkinson\u2019s Disease and the Efficacy of Antioxidant Treatment. Antioxidants, 13.","DOI":"10.3390\/antiox13091138"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Chakrabarti, S., and Bisaglia, M. (2023). Oxidative Stress and Neuroinflammation in Parkinson\u2019s Disease: The Role of Dopamine Oxidation Products. Antioxidants, 12.","DOI":"10.3390\/antiox12040955"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105798","DOI":"10.1016\/j.neuint.2024.105798","article-title":"Combating Parkinson\u2019s Disease with Plant-Derived Polyphenols: Targeting Oxidative Stress and Neuroinflammation","volume":"178","author":"Gahtani","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gusti, A.M.T., Qusti, S.Y., Alshammari, E.M., Toraih, E.A., and Fawzy, M.S. (2021). Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study. Antioxidants, 10.","DOI":"10.3390\/antiox10040595"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","article-title":"Astrocytes: Biology and Pathology","volume":"119","author":"Sofroniew","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.freeradbiomed.2016.06.027","article-title":"Adaptive Regulation of the Brain\u2019s Antioxidant Defences by Neurons and Astrocytes","volume":"100","author":"Baxter","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/nm.4397","article-title":"Microglia Emerge as Central Players in Brain Disease","volume":"23","author":"Salter","year":"2017","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1742-2094-5-8","article-title":"Neuroinflammation Mediated by IL-1\u03b2 Increases Susceptibility of Dopamine Neurons to Degeneration in an Animal Model of Parkinson\u2019s Disease","volume":"5","author":"Koprich","year":"2008","journal-title":"J. Neuroinflammation"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in Neurodegenerative Diseases: Mechanism and Potential Therapeutic Targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Du, X., Xie, X., and Liu, R. (2020). The Role of \u03b1-Synuclein Oligomers in Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228645"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Li, Y., Xia, Y., Yin, S., Wan, F., Hu, J., Kou, L., Sun, Y., Wu, J., Zhou, Q., and Huang, J. (2021). Targeting Microglial \u03b1-Synuclein\/TLRs\/NF-kappaB\/NLRP3 Inflammasome Axis in Parkinson\u2019s Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.719807"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-G\u00f3mez, J.A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M.K.R., Herrera, A.J., Espinosa-Oliva, A.M., Joseph, B., Hajji, N., Venero, J.L., and Burguillos, M.A. (2020). Microglia: Agents of the CNS Pro-Inflammatory Response. Cells, 9.","DOI":"10.3390\/cells9071717"},{"key":"ref_70","first-page":"2721","article-title":"Metabolic Dysregulation in Parkinson\u2019s Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism","volume":"16","author":"Pokotylo","year":"2025","journal-title":"Aging Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1002\/ana.410360612","article-title":"Complex I, Iron, and Ferritin in Parkinson\u2019s Disease Substantia Nigra","volume":"36","author":"Mann","year":"1994","journal-title":"Ann. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11515-017-1450-6","article-title":"Succinate Dehydrogenase in Parkinson\u2019s Disease","volume":"12","author":"Farshbaf","year":"2017","journal-title":"Front. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1038\/s41598-020-79339-2","article-title":"Inhibition of Mitochondrial Complex II in Neuronal Cells Triggers Unique Pathways Culminating in Autophagy with Implications for Neurodegeneration","volume":"11","author":"Ranganayaki","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S155","DOI":"10.1002\/mds.22781","article-title":"Mitochondrial Therapies for Parkinson\u2019s Disease","volume":"25","author":"Thomas","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.chembiol.2023.06.018","article-title":"S-Nitrosylation-Mediated Dysfunction of TCA Cycle Enzymes in Synucleinopathy Studied in Postmortem Human Brains and hiPSC-Derived Neurons","volume":"30","author":"Doulias","year":"2023","journal-title":"Cell Chem. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/brain\/115.2.333","article-title":"Brain, skeletal muscle and platelet homogenate mitochondrial function in parkinson\u2019s disease","volume":"115","author":"Mann","year":"1992","journal-title":"Brain"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41531-025-01099-5","article-title":"Urea Cycle Dysregulation Drives Metabolic Stress and Neurodegeneration in Parkinson\u2019s Disease","volume":"11","author":"Zhang","year":"2025","journal-title":"npj Park. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Higashi, A., Mizutani, Y., Ohdake, R., Maeda, Y., Yoshimoto, J., Shima, S., Seino, Y., Ueda, A., Ito, M., and Suzuki, A. (2025). Metabolic Profiles Associated with Fat Loss in Parkinson\u2019s Disease. J. Neurol. Neurosurg. Psychiatry, jnnp-2025-336929.","DOI":"10.1136\/jnnp-2025-336929"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Huang, H.-Y., Tsao, S.-P., and Yeh, T.-H. (2025). Branched-Chain Amino Acids in Parkinson\u2019s Disease: Molecular Mechanisms and Therapeutic Potential. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26146992"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ceb.2017.03.013","article-title":"PINK1 and Parkin: Emerging Themes in Mitochondrial Homeostasis","volume":"45","author":"McWilliams","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"100209","DOI":"10.1074\/jbc.REV120.014294","article-title":"Targeting Mitophagy in Parkinson\u2019s Disease","volume":"296","author":"Clark","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.neurobiolaging.2013.11.008","article-title":"The Mitochondrial Permeability Transition Pore Regulates Parkinson\u2019s Disease Development in Mutant \u03b1-Synuclein Transgenic Mice","volume":"35","author":"Martin","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_83","first-page":"423","article-title":"Serum Tyrosine-to-Phenylalanine Ratio Is Low in Parkinson\u2019s Disease","volume":"6","author":"Hirayama","year":"2016","journal-title":"J. Park. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.tcb.2017.01.005","article-title":"The Interplay of Axonal Energy Homeostasis and Mitochondrial Trafficking and Anchoring","volume":"27","author":"Sheng","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.cell.2011.10.018","article-title":"PINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility","volume":"147","author":"Wang","year":"2011","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0306-4522(01)00562-0","article-title":"Involvement of Inducible Nitric Oxide Synthase in Inflammation-Induced Dopaminergic Neurodegeneration","volume":"110","author":"Iravani","year":"2002","journal-title":"Neuroscience"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1093\/brain\/awm318","article-title":"The Role of Autophagy-Lysosome Pathway in Neurodegeneration Associated with Parkinson\u2019s Disease","volume":"131","author":"Pan","year":"2008","journal-title":"Brain"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainresbull.2017.03.009","article-title":"Metabolic Dysfunction in Parkinson\u2019s Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism","volume":"133","author":"Anandhan","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"110672","DOI":"10.1016\/j.brainresbull.2023.110672","article-title":"Glucose Metabolism Impairment in Parkinson\u2019s Disease","volume":"199","author":"Dai","year":"2023","journal-title":"Brain Res. Bull."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2011.06.001","article-title":"Gaucher Disease Glucocerebrosidase and \u03b1-Synuclein Form a Bidirectional Pathogenic Loop in Synucleinopathies","volume":"146","author":"Mazzulli","year":"2011","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/jnc.14908","article-title":"Leucine-rich Repeat Kinase 2 and Lysosomal Dyshomeostasis in Parkinson Disease","volume":"152","author":"Cogo","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1213\/ANE.0000000000007096","article-title":"Links Between Cellular Energy Metabolism and Pain Sensation","volume":"140","author":"Li","year":"2025","journal-title":"Anesth. Analg."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"115167","DOI":"10.1016\/j.expneurol.2025.115167","article-title":"Targeting the NLRP3 Inflammasome in Parkinson\u2019s Disease: From Molecular Mechanism to Therapeutic Strategy","volume":"386","author":"Liang","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_94","first-page":"617472","article-title":"Mitochondrial Dysfunction in Parkinson\u2019s Disease: Pathogenesis and Neuroprotection","volume":"2011","author":"Mounsey","year":"2011","journal-title":"Park. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.cell.2016.11.018","article-title":"Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson\u2019s Disease","volume":"167","author":"Sampson","year":"2016","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/CM9.0000000000003318","article-title":"Gut Microbiota and Parkinson\u2019s Disease","volume":"138","author":"Wang","year":"2025","journal-title":"Chin. Med. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s00702-025-02893-4","article-title":"Levodopa Treatment: Impacts and Mechanisms throughout Parkinson\u2019s Disease Progression","volume":"132","author":"Riederer","year":"2025","journal-title":"J. Neural Transm."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1212\/WNL.0000000000012868","article-title":"Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary: A Report of the AAN Guideline Subcommittee","volume":"97","author":"Pringsheim","year":"2021","journal-title":"Neurology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1021\/acschemneuro.8b00291","article-title":"Design, Synthesis, and Pharmacological Characterization of Carbazole Based Dopamine Agonists as Potential Symptomatic and Neuroprotective Therapeutic Agents for Parkinson\u2019s Disease","volume":"10","author":"Elmabruk","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0140-6736(23)01429-0","article-title":"Medical, Surgical, and Physical Treatments for Parkinson\u2019s Disease","volume":"403","author":"Foltynie","year":"2024","journal-title":"Lancet"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/mds.25751","article-title":"Randomized Trial of Safinamide Add-on to Levodopa in Parkinson\u2019s Disease with Motor Fluctuations","volume":"29","author":"Borgohain","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1001\/jamaneurol.2016.4467","article-title":"Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients with Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial","volume":"74","author":"Schapira","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"29","DOI":"10.5334\/tohm.712","article-title":"Tremor in Parkinson\u2019s Disease: From Pathophysiology to Advanced Therapies","volume":"12","author":"Abusrair","year":"2022","journal-title":"Tremor Other Hyperkinetic Mov."},{"key":"ref_104","first-page":"CD003735","article-title":"Anticholinergics for Symptomatic Management of Parkinson\u2019s Disease","volume":"2","author":"Katzenschlager","year":"2002","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"32","DOI":"10.9740\/mhc.2022.01.032","article-title":"Istradefylline: A Novel Agent in the Treatment of \u201coff\u201d Episodes Associated with Levodopa\/Carbidopa Use in Parkinson Disease","volume":"12","author":"Cummins","year":"2022","journal-title":"Ment. Health Clin."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s11082-023-06125-5","article-title":"DFT and QSAR Study of Catechol-O-Methyltransferase (COMT) as Inhibitors for Parkinson\u2019s Disease Treatment","volume":"56","author":"Sherif","year":"2024","journal-title":"Opt. Quantum Electron."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1590\/0004-282x-anp-2021-0219","article-title":"Guidelines for Parkinson\u2019s Disease Treatment: Consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology\u2014Motor Symptoms","volume":"80","author":"Saba","year":"2022","journal-title":"Arq. Neuro-Psiquiatr."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1001\/jama.2008.929","article-title":"Bilateral Deep Brain Stimulation vs. Best Medical Therapy for Patients with Advanced Parkinson DiseaseA Randomized Controlled Trial","volume":"301","author":"Weaver","year":"2009","journal-title":"JAMA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1056\/NEJMoa2016311","article-title":"Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson\u2019s Disease","volume":"383","author":"Shah","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1056\/NEJMoa2202721","article-title":"Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson\u2019s Disease","volume":"388","author":"Krishna","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_111","first-page":"CD013856","article-title":"Physical Exercise for People with Parkinson\u2019s Disease: A Systematic Review and Network Meta-Analysis","volume":"2","author":"Ernst","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1001\/jamaneurol.2016.4703","article-title":"Opicapone as Adjunct to Levodopa Therapy in Patients with Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial","volume":"74","author":"Lees","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Piccinin, E., Sardanelli, A.M., Seibel, P., Moschetta, A., Cocco, T., and Villani, G. (2021). PGC-1s in the Spotlight with Parkinson\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073487"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13024-020-00363-x","article-title":"PARIS Induced Defects in Mitochondrial Biogenesis Drive Dopamine Neuron Loss under Conditions of Parkin or PINK1 Deficiency","volume":"15","author":"Pirooznia","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_115","first-page":"2117","article-title":"Role of NLRP3 Inflammasome in Parkinson\u2019s Disease and Therapeutic Considerations","volume":"12","author":"Nguyen","year":"2022","journal-title":"J. Park. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1212\/WNL.0000000000009107","article-title":"Disease Modification and Biomarker Development in Parkinson Disease: Revision or Reconstruction?","volume":"94","author":"Espay","year":"2020","journal-title":"Neurology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S1474-4422(21)00061-2","article-title":"Progress towards Therapies for Disease Modification in Parkinson\u2019s Disease","volume":"20","author":"Vijiaratnam","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"eabo1997","DOI":"10.1126\/scitranslmed.abo1997","article-title":"Single-Cell Transcriptomic and Proteomic Analysis of Parkinson\u2019s Disease Brains","volume":"16","author":"Zhu","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Dumitriu, A., Golji, J., Labadorf, A.T., Gao, B., Beach, T.G., Myers, R.H., Longo, K.A., and Latourelle, J.C. (2015). Integrative Analyses of Proteomics and RNA Transcriptomics Implicate Mitochondrial Processes, Protein Folding Pathways and GWAS Loci in Parkinson Disease. BMC Med. Genom., 9.","DOI":"10.1186\/s12920-016-0164-y"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1093\/brain\/awab446","article-title":"Single-Cell Sequencing of Human Midbrain Reveals Glial Activation and a Parkinson-Specific Neuronal State","volume":"145","author":"Landoulsi","year":"2022","journal-title":"Brain"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s40478-020-00932-7","article-title":"Common Gene Expression Signatures in Parkinson\u2019s Disease Are Driven by Changes in Cell Composition","volume":"8","author":"Nido","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41593-022-01061-1","article-title":"Single-Cell Genomic Profiling of Human Dopamine Neurons Identifies a Population That Selectively Degenerates in Parkinson\u2019s Disease","volume":"25","author":"Kamath","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1212\/WNL.0000000000004516","article-title":"Analysis of Blood-Based Gene Expression in Idiopathic Parkinson Disease","volume":"89","author":"Shamir","year":"2017","journal-title":"Neurology"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Calligaris, R., Banica, M., Roncaglia, P., Robotti, E., Finaurini, S., Vlachouli, C., Antonutti, L., Iorio, F., Carissimo, A., and Cattaruzza, T. (2015). Blood Transcriptomics of Drug-Na\u00efve Sporadic Parkinson\u2019s Disease Patients. BMC Genom., 16.","DOI":"10.1186\/s12864-015-2058-3"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e00762","DOI":"10.1016\/j.neurot.2025.e00762","article-title":"Whole Transcriptome Analysis of Peripheral Blood Mononuclear Cells from de Novo and Drug-Naive Parkinson\u2019s Disease Patients","volume":"22","author":"Navarrete","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13024-023-00699-0","article-title":"Unravelling Cell Type-Specific Responses to Parkinson\u2019s Disease at Single Cell Resolution","volume":"19","author":"Martirosyan","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s Disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Dias Pinto, J.R., Faustinoni Neto, B., Munhoz, L., Kerkis, I., and Araldi, R.P. (2025). From Brain to Blood: Uncovering Potential Therapeutical Targets and Biomarkers for Huntington\u2019s Disease Using an Integrative RNA-Seq Analytical Platform (BDASeq\u00ae). Cells, 14.","DOI":"10.3390\/cells14130976"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"25763","DOI":"10.1038\/s41598-024-77401-x","article-title":"Druggable Targets for Parkinson\u2019s Disease: Transcriptomics Based Mendelian Randomization Study","volume":"14","author":"Lyu","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: A Revolutionary Tool for Transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13045-023-01494-6","article-title":"Advances in Single-Cell RNA Sequencing and Its Applications in Cancer Research","volume":"16","author":"Huang","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"29","DOI":"10.17311\/pharma.2023.29.39","article-title":"Pharma Data Analytics (Pharma Intelligence): Opportunities and Challenges in the Multi-Omics Era of Drug Discovery and Development","volume":"14","author":"Neto","year":"2023","journal-title":"Pharmacologia"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13059-016-0881-8","article-title":"A Survey of Best Practices for RNA-Seq Data Analysis","volume":"17","author":"Conesa","year":"2016","journal-title":"Genome Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"27086","DOI":"10.1038\/s41598-025-09417-w","article-title":"Single Nucleus RNA Sequencing Profile Analysis to Reveal Cell Type Specific Common Molecular Drivers of Parkinson\u2019s Disease and Therapeutic Agents","volume":"15","author":"Pappu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Semenova, E.I., Vlasov, I.N., Partevian, S.A., Rosinskaya, A.V., Rybolovlev, I.N., Slominsky, P.A., Shadrina, M.I., and Alieva, A.K. (2022). Transcriptome Profiling Reveals Differential Expression of Circadian Behavior Genes in Peripheral Blood of Monozygotic Twins Discordant for Parkinson\u2019s Disease. Cells, 11.","DOI":"10.3390\/cells11162599"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e25888","DOI":"10.1097\/MD.0000000000025888","article-title":"RNA-Sequencing of Peripheral Blood Circular RNAs in Parkinson Disease","volume":"100","author":"Kong","year":"2021","journal-title":"Medicine"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"12191","DOI":"10.18632\/aging.205954","article-title":"Aging-Related Biomarkers for the Diagnosis of Parkinson\u2019s Disease Based on Bioinformatics Analysis and Machine Learning","volume":"16","author":"Yang","year":"2024","journal-title":"Aging"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"0300060520957197","DOI":"10.1177\/0300060520957197","article-title":"Identification of Parkinson\u2019s Disease-Related Pathways and Potential Risk Factors","volume":"48","author":"Shen","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41531-024-00790-3","article-title":"Single-Cell RNA Sequencing Reveals Peripheral Immunological Features in Parkinson\u2019s Disease","volume":"10","author":"Xiong","year":"2024","journal-title":"npj Park. Dis."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Henderson, A.R., Wang, Q., Meechoovet, B., Siniard, A.L., Naymik, M., De Both, M., Huentelman, M.J., Caselli, R.J., Driver-Dunckley, E., and Dunckley, T. (2021). DNA Methylation and Expression Profiles of Whole Blood in Parkinson\u2019s Disease. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.640266"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1038\/s41598-021-81961-7","article-title":"Inflammation and Regulatory T Cell Genes Are Differentially Expressed in Peripheral Blood Mononuclear Cells of Parkinson\u2019s Disease Patients","volume":"11","author":"Karaaslan","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"106891","DOI":"10.1016\/j.nbd.2025.106891","article-title":"Exploring the Dynamic Pathogenesis of Parkinson\u2019s Disease by Case-Control and Longitudinal Blood Transcriptome Analyses","volume":"209","author":"Xue","year":"2025","journal-title":"Neurobiol. Dis."},{"key":"ref_143","first-page":"25","article-title":"Transcriptome Analysis Reveals a Two-Gene Signature Links to Motor Progression and Alterations of Immune Cells in Parkinson\u2019s Disease","volume":"13","author":"Li","year":"2022","journal-title":"J. Park. Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1177\/1535370220967325","article-title":"Transcriptomic Profiles in Parkinson\u2019s Disease","volume":"246","author":"Kurvits","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"ref_145","first-page":"109","article-title":"Transcriptomic Profiling of Extracellular RNAs Present in Cerebrospinal Fluid Identifies Differentially Expressed Transcripts in Parkinson\u2019s Disease","volume":"6","author":"Fatemi","year":"2016","journal-title":"J. Park. Dis."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1007\/s10571-023-01334-8","article-title":"A Pilot Study of Ex Vivo Human Prefrontal RNA Transcriptomics in Parkinson\u2019s Disease","volume":"43","author":"Lin","year":"2023","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Labadorf, A., Choi, S.H., and Myers, R.H. (2018). Evidence for a Pan-Neurodegenerative Disease Response in Huntington\u2019s and Parkinson\u2019s Disease Expression Profiles. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00430"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00401-023-02597-7","article-title":"Transcriptomic Profiling of Parkinson\u2019s Disease Brains Reveals Disease Stage Specific Gene Expression Changes","volume":"146","author":"Cappelletti","year":"2023","journal-title":"Acta Neuropathol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"104872","DOI":"10.1016\/j.nbd.2020.104872","article-title":"Expanding the Search for Genetic Biomarkers of Parkinson\u2019s Disease into the Living Brain","volume":"140","author":"Benoit","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"106514","DOI":"10.1016\/j.nbd.2024.106514","article-title":"RNA Sequencing of Olfactory Bulb in Parkinson\u2019s Disease Reveals Gene Alterations Associated with Olfactory Dysfunction","volume":"196","author":"Tremblay","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3956","DOI":"10.1038\/s41467-023-39652-6","article-title":"Blood Transcriptomic Signatures Associated with Molecular Changes in the Brain and Clinical Outcomes in Parkinson\u2019s Disease","volume":"14","author":"Irmady","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Chi, J., Xie, Q., Jia, J., Liu, X., Sun, J., Deng, Y., and Yi, L. (2018). Integrated Analysis and Identification of Novel Biomarkers in Parkinson\u2019s Disease. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00178"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Xicoy, H., Brouwers, J.F., Wieringa, B., and Martens, G.J.M. (2020). Explorative Combined Lipid and Transcriptomic Profiling of Substantia Nigra and Putamen in Parkinson\u2019s Disease. Cells, 9.","DOI":"10.3390\/cells9091966"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"eadi8287","DOI":"10.1126\/sciadv.adi8287","article-title":"Molecular Profiling of Human Substantia Nigra Identifies Diverse Neuron Types Associated with Vulnerability in Parkinson\u2019s Disease","volume":"10","author":"Wang","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1007\/s10571-021-01146-8","article-title":"Multiomic Analyses of Dopaminergic Neurons Isolated from Human Substantia Nigra in Parkinson\u2019s Disease: A Descriptive and Exploratory Study","volume":"42","author":"Zaccaria","year":"2022","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Salemi, M., Ravo, M., Lanza, G., Schillaci, F.A., Ventola, G.M., Marchese, G., Salluzzo, M.G., Cappelletti, G., and Ferri, R. (2024). Gene Expression Profiling of Post Mortem Midbrain of Parkinson\u2019s Disease Patients and Healthy Controls. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020707"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Yao, X., Wang, P., Huang, Z., and Li, L. (2025). Differential Gene Expression and Immune Profiling in Parkinson\u2019s Disease: Unveiling Potential Candidate Biomarkers. BMC Neurol., 25.","DOI":"10.1186\/s12883-025-04388-x"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"pdb.top084970","DOI":"10.1101\/pdb.top084970","article-title":"RNA Sequencing and Analysis","volume":"2015","author":"Kukurba","year":"2015","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Corley, S.M., MacKenzie, K.L., Beverdam, A., Roddam, L.F., and Wilkins, M.R. (2017). Differentially Expressed Genes from RNA-Seq and Functional Enrichment Results Are Affected by the Choice of Single-End versus Paired-End Reads and Stranded versus Non-Stranded Protocols. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3797-0"},{"key":"ref_160","unstructured":"(2026, February 10). Andrews, Simon FastQC: A Quality Control Tool for High Throughput Sequence Data [Internet] 2010. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize Analysis Results for Multiple Tools and Samples in a Single Report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-Based Genome Alignment and Genotyping with HISAT2 and HISAT-Genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast Gapped-Read Alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12967-021-02936-w","article-title":"TPM, FPKM, or Normalized Counts? A Comparative Study of Quantification Measures for the Analysis of RNA-Seq Data from the NCI Patient-Derived Models Repository","volume":"19","author":"Zhao","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor Package for Differential Expression Analysis of Digital Gene Expression Data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/3\/254\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:36:45Z","timestamp":1772116605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/3\/254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":167,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cimb48030254"],"URL":"https:\/\/doi.org\/10.3390\/cimb48030254","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]}}}