{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:32:34Z","timestamp":1768566754632,"version":"3.49.0"},"posted":{"date-parts":[[2024,9,6]]},"group-title":"Neurology","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Objectives<\/jats:title>\n                  <jats:p>Excessive Manganese (Mn) exposure is neurotoxic and can cause Mn-Induced Parkinsonism (MnIP), marked by cognitive and motor dysfunction. Although metabolomic and lipidomic research in Parkinsonism (PD) patients exists, it remains limited. This study hypothesizes distinct metabolomic and lipidomic profiles based on exposure status, disease diagnosis, and their interaction.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used a case-control design with a 2\u00d72 factorial framework to investigate the metabolomic and lipidomic alterations associated with Mn exposure and their link to PD. The study population of 97 individuals was divided into four groups: non-exposed controls (n=23), exposed controls (n=25), non-exposed with PD (n=26) and exposed with PD (n=23). Cases, defined by at least two cardinal PD features (excluding vascular, iatrogenic, and traumatic origins), were recruited from movement disorder clinics in four hospitals in Brescia, Northern Italy. Controls, free from neurological or psychiatric conditions, were selected from the same hospitals. Exposed subjects resided in metallurgic regions (Val Camonica and Bagnolo Mella) for at least 8 continuous years, while non-exposed subjects lived in low-exposure areas around Lake Garda and Brescia city. We conducted untargeted analyses of metabolites and lipids in whole blood samples using ultra-high-performance liquid chromatography (UHPLC) and mass spectrometry (MS), followed by statistical analyses including Principal Component Analysis (PCA), Partial Least Squares\u2013Discriminant Analysis (PLS-DA), and Two-Way Analysis of Covariance (ANCOVA).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Metabolomic analysis revealed modulation of alanine, aspartate, and glutamate metabolism (Impact=0.05, p=0.001) associated with disease effect; butanoate metabolism (Impact=0.03, p=0.004) with the exposure effect; and vitamin B6 metabolism (Impact=0.08, p=0.03) with the interaction effect. Differential relative abundances in 3- sulfoxy-L-Tyrosine (\u03b2=1.12, FDR p&lt;0.001), glycocholic acid (\u03b2=0.48, FDR p=0.03), and palmitelaidic acid (\u03b2=0.30, FDR p&lt;0.001) were linked to disease, exposure, and interaction effects, respectively. In the lipidome, ferroptosis (Pathway Lipids=11, FDR p=0.03) associated with the disease effect and sphingolipid signaling (Pathway Lipids=9, FDR p=0.04) associated with the interaction effect were significantly altered. Lipid classes triacylglycerols, ceramides, and phosphatidylethanolamines showed differential relative abundances associated with disease, exposure, and interaction effects, respectively.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>These findings suggest that PD and Mn exposure induce unique metabolomic and lipidomic changes, potentially serving as biomarkers for MnIP and warranting further study.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.04.24313002","type":"posted-content","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T13:20:38Z","timestamp":1725628838000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolomic and Lipidomic Analysis of Manganese-Associated Parkinsonism: a Case-Control Study in Brescia, Italy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5606-8926","authenticated-orcid":false,"given":"Freeman","family":"Lewis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Shoieb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4951-614X","authenticated-orcid":false,"given":"Somaiyeh","family":"Azmoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1875-8448","authenticated-orcid":false,"given":"Elena","family":"Colicino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhua","family":"Chi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7598-5022","authenticated-orcid":false,"given":"Haiwei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1606-5397","authenticated-orcid":false,"given":"Donatella","family":"Placidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-3639","authenticated-orcid":false,"given":"Alessandro","family":"Padovani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-6606","authenticated-orcid":false,"given":"Andrea","family":"Pilotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulvio","family":"Pepe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinella","family":"Turla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Crippa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-2608","authenticated-orcid":false,"given":"Xuexia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-0237","authenticated-orcid":false,"given":"Roberto G","family":"Lucchini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024090903300543000_2024.09.04.24313002v1.1","doi-asserted-by":"crossref","unstructured":"Abdelzaher, H. , et al., Climate change, human health, and the exposome: Utilizing OMIC technologies to navigate an era of uncertainty. Frontiers in Public Health, 2022. 10.","DOI":"10.3389\/fpubh.2022.973000"},{"issue":"12","key":"2024090903300543000_2024.09.04.24313002v1.2","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.3390\/microorganisms10122411","article-title":"Manganese Pollution and Its Remediation: A Review of Biological Removal and Promising Combination Strategies","volume":"10","year":"2022","journal-title":"Microorganisms"},{"key":"2024090903300543000_2024.09.04.24313002v1.3","unstructured":"[EPA], E.P.A., The Fourth Unregulated Contaminant Monitoring Rule (UCMR 4): Data Summary. 2022, Office of Water (MS-140): Washington, D.C."},{"key":"2024090903300543000_2024.09.04.24313002v1.4","doi-asserted-by":"crossref","unstructured":"Song, J. , et al., Building Better Full Manganese-Based Cathode Materials for Next-Generation Lithium-Ion Batteries. Electrochemical Energy Reviews, 2023. 6(1).","DOI":"10.1007\/s41918-023-00184-8"},{"key":"2024090903300543000_2024.09.04.24313002v1.5","doi-asserted-by":"crossref","unstructured":"Wang, P. , et al., Efficiency stagnation in global steel production urges joint supply- and demand-side mitigation efforts. Nature Communications, 2021. 12(1).","DOI":"10.1038\/s41467-021-22245-6"},{"key":"2024090903300543000_2024.09.04.24313002v1.6","doi-asserted-by":"crossref","unstructured":"Xu, C. , et al., Future material demand for automotive lithium-based batteries. Communications Materials, 2020. 1(1).","DOI":"10.1038\/s43246-020-00095-x"},{"issue":"24","key":"2024090903300543000_2024.09.04.24313002v1.7","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.3390\/cells12242842","article-title":"Signaling Pathways Involved in Manganese-Induced Neurotoxicity","volume":"12","year":"2023","journal-title":"Cells"},{"issue":"2","key":"2024090903300543000_2024.09.04.24313002v1.8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.14802\/jmd.20123","article-title":"Manganese and Movement Disorders: A Review","volume":"14","year":"2021","journal-title":"J Mov Disord"},{"key":"2024090903300543000_2024.09.04.24313002v1.9","doi-asserted-by":"crossref","unstructured":"Pajarillo, E. , et al., Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies. Frontiers in Pharmacology, 2022. 13.","DOI":"10.3389\/fphar.2022.1011947"},{"key":"2024090903300543000_2024.09.04.24313002v1.10","first-page":"100057","article-title":"Parkinsonism and chronic manganese exposure: Pilot study with clinical, environmental and experimental evidence","volume":"3","year":"2020","journal-title":"Clin Park Relat Disord"},{"key":"2024090903300543000_2024.09.04.24313002v1.11","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.20494"},{"key":"2024090903300543000_2024.09.04.24313002v1.12","doi-asserted-by":"crossref","unstructured":"Racette, B.A. , et al., Severity of parkinsonism associated with environmental manganese exposure. Environmental Health, 2021. 20(1).","DOI":"10.1186\/s12940-021-00712-3"},{"issue":"8","key":"2024090903300543000_2024.09.04.24313002v1.13","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.3390\/biom13081190","article-title":"Manganese-Induced Parkinsonism: Evidence from Epidemiological and Experimental Studies","volume":"13","year":"2023","journal-title":"Biomolecules"},{"issue":"8","key":"2024090903300543000_2024.09.04.24313002v1.14","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1097\/JOM.0000000000001634","article-title":"MRI Signal Intensity and Parkinsonism in Manganese- Exposed Workers","volume":"61","year":"2019","journal-title":"J Occup Environ Med"},{"key":"2024090903300543000_2024.09.04.24313002v1.15","doi-asserted-by":"crossref","first-page":"115238","DOI":"10.1016\/j.ecoenv.2023.115238","article-title":"Manganese overexposure induces Parkinson-like symptoms, altered lipid signature and oxidative stress in C57BL\/6 J mouse","volume":"263","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"issue":"2","key":"2024090903300543000_2024.09.04.24313002v1.16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3892\/mi.2024.135","article-title":"Diagnosis of manganism and manganese neurotoxicity: A workshop report","volume":"4","year":"2024","journal-title":"Med Int (Lond"},{"key":"2024090903300543000_2024.09.04.24313002v1.17","doi-asserted-by":"crossref","unstructured":"Gonzalez-Covarrubias, V. , E. Mart\u00ednez-Mart\u00ednez , and L. Del Bosque-Plata , The Potential of Metabolomics in Biomedical Applications. Metabolites, 2022. 12(2).","DOI":"10.3390\/metabo12020194"},{"key":"2024090903300543000_2024.09.04.24313002v1.18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jtemb.2018.11.001","article-title":"The reproducibility of urinary ions in manganese exposed workers","volume":"51","year":"2019","journal-title":"Journal of Trace Elements in Medicine and Biology"},{"key":"2024090903300543000_2024.09.04.24313002v1.19","doi-asserted-by":"crossref","unstructured":"Carter, K.A. , et al., Short Report: Using Targeted Urine Metabolomics to Distinguish Between Manganese Exposed and Unexposed Workers in a Small Occupational Cohort. Frontiers in Public Health, 2021. 9.","DOI":"10.3389\/fpubh.2021.666787"},{"issue":"1","key":"2024090903300543000_2024.09.04.24313002v1.20","doi-asserted-by":"crossref","first-page":"17635","DOI":"10.1038\/s41598-020-74823-1","article-title":"Predicting human health from biofluid-based metabolomics using machine learning","volume":"10","year":"2020","journal-title":"Scientific Reports"},{"key":"2024090903300543000_2024.09.04.24313002v1.21","doi-asserted-by":"crossref","unstructured":"Lucchini, R.G. , et al., Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism. Frontiers in Neurology, 2020. 11.","DOI":"10.3389\/fneur.2020.556337"},{"issue":"1","key":"2024090903300543000_2024.09.04.24313002v1.22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.toxlet.2014.06.019","article-title":"Manganese accumulation in bone following chronic exposure in rats: Steady-state concentration and half-life in bone","volume":"229","year":"2014","journal-title":"Toxicology Letters"},{"issue":"2","key":"2024090903300543000_2024.09.04.24313002v1.23","first-page":"143123","article-title":"Profiles and species of Mn, Fe and trace metals in soils near a ferromanganese plant in Bagnolo Mella (Brescia, IT)","volume":"755","year":"2021","journal-title":". Sci Total Environ"},{"issue":"4","key":"2024090903300543000_2024.09.04.24313002v1.24","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/jes.2014.70","article-title":"Manganese concentrations in soil and settled dust in an area with historic ferroalloy production","volume":"25","year":"2015","journal-title":"Journal of Exposure Science & Environmental Epidemiology"},{"key":"2024090903300543000_2024.09.04.24313002v1.25","doi-asserted-by":"publisher","DOI":"10.1289\/EHP13435"},{"key":"2024090903300543000_2024.09.04.24313002v1.26","doi-asserted-by":"crossref","unstructured":"Jin, Y. , et al., Recent Review on Selected Xenobiotics and Their Impacts on Gut Microbiome and Metabolome. Trends Analyt Chem, 2023. 166.","DOI":"10.1016\/j.trac.2023.117155"},{"issue":"2","key":"2024090903300543000_2024.09.04.24313002v1.27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/toxsci\/kfad056","article-title":"Maternal PBDE exposure disrupts gut microbiome and promotes hepatic proinflammatory signaling in humanized PXR-transgenic mouse offspring over time","volume":"194","year":"2023","journal-title":"Toxicol Sci"},{"issue":"1","key":"2024090903300543000_2024.09.04.24313002v1.28","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1038\/s41467-024-48355-5","article-title":"Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction","volume":"15","year":"2024","journal-title":"Nat Commun"},{"key":"2024090903300543000_2024.09.04.24313002v1.29","doi-asserted-by":"crossref","unstructured":"Scieszka, D.P. , et al., Multi-omic assessment shows dysregulation of pulmonary and systemic immunity to e-cigarette exposure. Respiratory Research, 2023. 24(1).","DOI":"10.1186\/s12931-023-02441-2"},{"key":"2024090903300543000_2024.09.04.24313002v1.30","doi-asserted-by":"crossref","unstructured":"Qiu, S. , et al., Small molecule metabolites: discovery of biomarkers and therapeutic targets. Signal Transduction and Targeted Therapy, 2023. 8(1).","DOI":"10.1038\/s41392-023-01399-3"},{"issue":"9","key":"2024090903300543000_2024.09.04.24313002v1.31","doi-asserted-by":"crossref","first-page":"e1009105","DOI":"10.1371\/journal.pcbi.1009105","article-title":"Pathway analysis in metabolomics: Recommendations for the use of over-representation analysis","volume":"17","year":"2021","journal-title":"PLOS Computational Biology"},{"key":"2024090903300543000_2024.09.04.24313002v1.32","doi-asserted-by":"crossref","unstructured":"Brooks, A ., Dysphagia and aspiration during a Parkinson\u2019s hospitalization: a care partner\u2019s perspective and recommendations for improving standards of care. Frontiers in Aging Neuroscience, 2023. 15.","DOI":"10.3389\/fnagi.2023.1258979"},{"issue":"3","key":"2024090903300543000_2024.09.04.24313002v1.33","doi-asserted-by":"crossref","first-page":"743","DOI":"10.3233\/JPD-213103","article-title":"Urinary Tract Infection in Parkinson\u2019s Disease","volume":"12","year":"2022","journal-title":"Journal of Parkinson\u2019s Disease"},{"key":"2024090903300543000_2024.09.04.24313002v1.34","unstructured":"Peechakara, B.V. and M. Gupta , Ampicillin\/Sulbactam , in StatPearls. 2024, StatPearls PublishingCopyright \u00a9 2024, StatPearls Publishing LLC.: Treasure Island (FL)."},{"issue":"5480","key":"2024090903300543000_2024.09.04.24313002v1.35","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/252237a0","article-title":"Dopamine 3-O-sulphate, an end product of L-dopa metabolism in Parkinson patients","volume":"252","year":"1974","journal-title":"Nature"},{"issue":"11","key":"2024090903300543000_2024.09.04.24313002v1.36","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1212\/WNL.42.11.2111","article-title":"Markers of dopamine metabolism in Parkinson\u2019s disease. The Parkinson Study Group","volume":"42","year":"1992","journal-title":"Neurology"},{"key":"2024090903300543000_2024.09.04.24313002v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2011.05.050"},{"issue":"3","key":"2024090903300543000_2024.09.04.24313002v1.38","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.3390\/ijms24031817","article-title":"Overview of the Role of Vanillin in Neurodegenerative Diseases and Neuropathophysiological Conditions","volume":"24","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"key":"2024090903300543000_2024.09.04.24313002v1.39","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.sbi.2019.12.002","article-title":"Emerging patterns of tyrosine sulfation and O-glycosylation cross-talk and co-localization","volume":"62","year":"2020","journal-title":"Curr Opin Struct Biol"},{"issue":"1","key":"2024090903300543000_2024.09.04.24313002v1.40","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2047-9158-1-4","article-title":"Norepinephrine: the next therapeutics frontier for Parkinson\u2019s disease","volume":"1","year":"2012","journal-title":"Translational Neurodegeneration"},{"key":"2024090903300543000_2024.09.04.24313002v1.41","doi-asserted-by":"crossref","unstructured":"Rekik, A. , et al., Parkinson\u2019s disease and vitamins: a focus on vitamin B12. Journal of Neural Transmission, 2024.","DOI":"10.1007\/s00702-024-02769-z"},{"key":"2024090903300543000_2024.09.04.24313002v1.42","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20149399"},{"issue":"38","key":"2024090903300543000_2024.09.04.24313002v1.43","doi-asserted-by":"crossref","first-page":"10853","DOI":"10.3748\/wjg.v21.i38.10853","article-title":"Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction","volume":"21","year":"2015","journal-title":"World J Gastroenterol"},{"key":"2024090903300543000_2024.09.04.24313002v1.44","doi-asserted-by":"crossref","unstructured":"Reimer, L. , et al., Low dose DMSO treatment induces oligomerization and accelerates aggregation of \u03b1-synuclein. Scientific Reports, 2022. 12(1).","DOI":"10.1038\/s41598-022-07706-2"},{"key":"2024090903300543000_2024.09.04.24313002v1.45","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003663"},{"key":"2024090903300543000_2024.09.04.24313002v1.46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191670"},{"key":"2024090903300543000_2024.09.04.24313002v1.47","doi-asserted-by":"publisher","DOI":"10.1254\/fpj.117.377"},{"key":"2024090903300543000_2024.09.04.24313002v1.48","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.01.070181.002253"},{"issue":"12","key":"2024090903300543000_2024.09.04.24313002v1.49","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.3390\/antiox11122467","article-title":"Association between Heavy Metal Exposure and Parkinson\u2019s Disease: A Review of the Mechanisms Related to Oxidative Stress","volume":"11","year":"2022","journal-title":"Antioxidants"},{"issue":"5","key":"2024090903300543000_2024.09.04.24313002v1.50","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1016\/0016-5085(92)91735-M","article-title":"Glycocholic acid and glycodeoxycholic acid but not glycoursocholic acid inhibit bile acid synthesis in the rabbit","volume":"102","year":"1992","journal-title":"Gastroenterology"},{"key":"2024090903300543000_2024.09.04.24313002v1.51","doi-asserted-by":"crossref","unstructured":"Troisi, J. , et al., A metabolomic signature of treated and drug-na\u00efve patients with Parkinson\u2019s disease: a pilot study. Metabolomics, 2019. 15(6).","DOI":"10.1007\/s11306-019-1554-x"},{"issue":"2","key":"2024090903300543000_2024.09.04.24313002v1.52","doi-asserted-by":"crossref","first-page":"174","DOI":"10.9758\/cpn.2020.18.2.174","article-title":"The Role of the SLC Transporters Protein in the Neurodegenerative Disorders","volume":"18","year":"2020","journal-title":"Clin Psychopharmacol Neurosci"},{"issue":"19","key":"2024090903300543000_2024.09.04.24313002v1.53","doi-asserted-by":"crossref","first-page":"6060","DOI":"10.3390\/molecules26196060","article-title":"Heavy Metals and Human Health: Possible Exposure Pathways and the Competition for Protein Binding Sites","volume":"26","year":"2021","journal-title":"Molecules"},{"issue":"2","key":"2024090903300543000_2024.09.04.24313002v1.54","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/acel.12546","article-title":"Dimethyl sulfide protects against oxidative stress and extends lifespan via a methionine sulfoxide reductase A-dependent catalytic mechanism","volume":"16","year":"2017","journal-title":"Aging Cell"},{"issue":"3","key":"2024090903300543000_2024.09.04.24313002v1.55","doi-asserted-by":"crossref","first-page":"943","DOI":"10.3390\/ijerph17030943","article-title":"Associations between Cadmium Exposure and Taste and Smell Dysfunction: Results from the National Health and Nutrition Examination Survey (NHANES), 2011\u20132014","volume":"17","year":"2020","journal-title":"International Journal of Environmental Research and Public Health"},{"issue":"2","key":"2024090903300543000_2024.09.04.24313002v1.56","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ncl.2008.03.017","article-title":"Updates in the management of seizures and status epilepticus in critically ill patients","volume":"26","year":"2008","journal-title":"Neurol Clin"},{"key":"2024090903300543000_2024.09.04.24313002v1.57","unstructured":"Information, N.C.f.B., PubChem Compound Summary for CID 7284, 2- Methylbutyraldehyde. 2024."},{"issue":"2","key":"2024090903300543000_2024.09.04.24313002v1.58","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3390\/metabo9020031","article-title":"Palmitate and Stearate are Increased in the Plasma in a 6-OHDA Model of Parkinson\u2019s Disease","volume":"9","year":"2019","journal-title":"Metabolites"},{"key":"2024090903300543000_2024.09.04.24313002v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(95)05696-3"},{"key":"2024090903300543000_2024.09.04.24313002v1.60","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/63.3.306"},{"issue":"16","key":"2024090903300543000_2024.09.04.24313002v1.61","doi-asserted-by":"crossref","first-page":"3585","DOI":"10.3390\/nu15163585","article-title":"The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson\u2019s Disease Pathogenesis","volume":"15","year":"2023","journal-title":"Nutrients"},{"issue":"12","key":"2024090903300543000_2024.09.04.24313002v1.62","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.3390\/biomedicines10123250","article-title":"The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease","volume":"10","year":"2022","journal-title":"Biomedicines"},{"key":"2024090903300543000_2024.09.04.24313002v1.63","doi-asserted-by":"publisher","DOI":"10.3390\/nu13062118"},{"key":"2024090903300543000_2024.09.04.24313002v1.64","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.522847"},{"key":"2024090903300543000_2024.09.04.24313002v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.06.002"},{"key":"2024090903300543000_2024.09.04.24313002v1.66","doi-asserted-by":"publisher","DOI":"10.3390\/cells11030395"},{"key":"2024090903300543000_2024.09.04.24313002v1.67","doi-asserted-by":"crossref","unstructured":"Fanning, S. , D. Selkoe , and U. Dettmer , Parkinson\u2019s disease: proteinopathy or lipidopathy? npj Parkinson\u2019s Disease, 2020. 6(1).","DOI":"10.1038\/s41531-019-0103-7"},{"key":"2024090903300543000_2024.09.04.24313002v1.68","doi-asserted-by":"crossref","unstructured":"Liu, Z. , et al., Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction. Nature Communications, 2022. 13(1).","DOI":"10.1038\/s41467-022-31168-9"},{"key":"2024090903300543000_2024.09.04.24313002v1.69","doi-asserted-by":"crossref","unstructured":"Liu, L. , et al., Ferroptosis-related factors in the substantia nigra are associated with Parkinson\u2019s disease. Scientific Reports, 2023. 13(1).","DOI":"10.1038\/s41598-023-42574-4"},{"key":"2024090903300543000_2024.09.04.24313002v1.70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/178910","article-title":"Sphingolipid Metabolic Pathway: An Overview of Major Roles Played in Human Diseases","volume":"2013","year":"2013","journal-title":"Journal of Lipids"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.09.04.24313002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:11:07Z","timestamp":1768507867000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2024.09.04.24313002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":70,"URL":"https:\/\/doi.org\/10.1101\/2024.09.04.24313002","relation":{},"subject":[],"published":{"date-parts":[[2024,9,6]]},"subtype":"preprint"}}