{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:47:47Z","timestamp":1793400467474,"version":"4.5.0"},"reference-count":207,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005088","name":"Beijing Municipal Health Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005088","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, with typical motor symptoms as the main clinical manifestations. At present, there are about 10 million patients with PD in the world, and its comorbidities and complications are numerous and incurable. Therefore, it is particularly important to explore the pathogenesis of PD and find possible therapeutic targets. Because the etiology of PD is complex, involving genes, environment, and aging, finding common factors is the key to identifying intervention targets. Hypoxia is ubiquitous in the natural environment and disease states, and it is considered to be closely related to the etiology of PD. Despite research showing that hypoxia increases the expression and aggregation of alpha-synuclein (\u03b1-syn), the most important pathogenic protein, there is still a lack of systematic studies on the role of hypoxia in \u03b1-syn pathology and PD pathogenesis. Considering that hypoxia is inextricably linked with various causes of PD, hypoxia may be a co-participant in many aspects of the PD pathologic process. In this review, we describe the risk factors for PD, and we discuss the possible role of hypoxia in inducing PD pathology by these risk factors. Furthermore, we attribute the pathological changes caused by PD etiology to oxygen uptake disorder and oxygen utilization disorder, thus emphasizing the possibility of hypoxia as a critical link in initiating or promoting \u03b1-syn pathology and PD pathogenesis. Our study provides novel insight for exploring the pathogenesis and therapeutic targets of PD.<\/jats:p>","DOI":"10.3389\/fnagi.2022.919343","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T05:01:57Z","timestamp":1658811717000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Hypoxia and Alpha-Synuclein: Inextricable Link Underlying the Pathologic Progression of Parkinson's Disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Mengyuan","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunming","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41572-021-00280-3","article-title":"Parkinson disease-associated cognitive impairment","volume":"7","author":"Aarsland","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0896-6273(00)80886-7","article-title":"Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system","volume":"25","author":"Abeliovich","year":"2000","journal-title":"Neuron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/s41422-019-0241-9","article-title":"Initiation of Parkinson's disease from gut to brain by delta-secretase","volume":"30","author":"Ahn","year":"2020","journal-title":"Cell Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4103\/bc.bc_46_19","article-title":"Role of vinpocetine in ischemic stroke and poststroke outcomes: a critical review","volume":"6","author":"Al-Kuraishy","year":"2020","journal-title":"Brain Circ."},{"key":"B5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nrgastro.2017.136","article-title":"Environmental triggers in IBD: a review of progress and evidence","volume":"15","author":"Ananthakrishnan","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1002\/hbm.20574","article-title":"Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation","volume":"30","author":"Ances","year":"2009","journal-title":"Hum. Brain Mapp."},{"key":"B7","doi-asserted-by":"publisher","first-page":"29739","DOI":"10.1074\/jbc.M600933200","article-title":"Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease","volume":"281","author":"Anderson","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1002\/bjs.10053","article-title":"Molecular and biological hallmarks of ageing","volume":"103","author":"Aunan","year":"2016","journal-title":"Br. J. Surg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jocn.2017.04.028","article-title":"Clinical effects of air pollution on the central nervous system; a review","volume":"43","author":"Babadjouni","year":"2017","journal-title":"J. Clin. Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"218","DOI":"10.3389\/fneur.2019.00218","article-title":"Parkinson's disease and the environment","volume":"10","author":"Ball","year":"2019","journal-title":"Front. Neurol."},{"key":"B11","first-page":"247","article-title":"Post-translational modification of \u03b1-synuclein in Parkinson's disease","volume-title":"Brain Res.","author":"Barrett","year":"2015"},{"key":"B12","doi-asserted-by":"publisher","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":"B13","doi-asserted-by":"publisher","first-page":"661117","DOI":"10.3389\/fneur.2021.661117","article-title":"Modulation of the interactions between \u03b1-synuclein and lipid membranes by post-translational modifications","volume":"12","author":"Bell","year":"2021","journal-title":"Front. Neurol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.neuron.2013.09.004","article-title":"The function of \u03b1-synuclein","volume":"79","author":"Bendor","year":"2013","journal-title":"Neuron"},{"key":"B15","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/s00401-017-1755-1","article-title":"Alpha-synuclein oligomers: a new hope","volume":"134","author":"Bengoa-Vergniory","year":"2017","journal-title":"Acta Neuropathol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1139\/H07-174","article-title":"Determinants of VO2 max decline with aging: an integrated perspective","volume":"33","author":"Betik","year":"2008","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"B17","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.parkreldis.2012.01.010","article-title":"Boxing and Parkinson disease: a link or a myth? An 18F-FDOPA PET\/CT study in retired Thai traditional boxers","volume":"18","author":"Bhidayasiri","year":"2012","journal-title":"Parkinsonism Relat. Disord."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1101\/gad.250167.114","article-title":"Human high-altitude adaptation: forward genetics meets the HIF pathway","volume":"28","author":"Bigham","year":"2014","journal-title":"Genes Dev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/S1474-4422(19)30287-X","article-title":"The genetic architecture of Parkinson's disease","volume":"19","author":"Blauwendraat","year":"2020","journal-title":"Lancet Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson's disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"759571","DOI":"10.3389\/fncel.2021.759571","article-title":"Functions of intracellular alpha-synuclein in microglia: implications for Parkinson's disease risk","volume":"15","author":"Booms","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.tins.2017.04.001","article-title":"The role of astrocyte dysfunction in Parkinson's disease pathogenesis","volume":"40","author":"Booth","year":"2017","journal-title":"Trends Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/jnc.13731","article-title":"Mitochondrial dysfunction in Parkinson's disease","volume":"139","author":"Bose","year":"2016","journal-title":"J. Neurochem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson's disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"B25","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1136\/thoraxjnl-2019-213738","article-title":"Role of unfolded proteins in lung disease","volume":"76","author":"Bradley","year":"2021","journal-title":"Thorax"},{"key":"B26","first-page":"305","article-title":"Astrocyte roles in traumatic brain injury","volume-title":"Exp. Neurol","author":"Burda","year":"2016"},{"key":"B27","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1002\/mds.28544","article-title":"Hypoxia conditioning as a promising therapeutic target in Parkinson's disease?","volume":"36","author":"Burtscher","year":"2021","journal-title":"Mov. Disord."},{"key":"B28","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1055\/s-0036-1585078","article-title":"Thrombolysis and thrombectomy for acute ischemic stroke: strengths and synergies","volume":"43","author":"Campbell","year":"2017","journal-title":"Semin. Thromb. Hemost."},{"key":"B29","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3389\/fimmu.2019.00239","article-title":"T-cell-driven inflammation as a mediator of the gut-brain axis involved in Parkinson's disease","volume":"10","author":"Campos-Acu\u00f1a","year":"2019","journal-title":"Front. Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e0197055","DOI":"10.1371\/journal.pone.0197055","article-title":"An investigation of cerebral oxygen utilization, blood flow and cognition in healthy aging","volume":"13","author":"Catchlove","year":"2018","journal-title":"PLoS ONE"},{"key":"B31","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00125-021-05380-z","article-title":"Hypoxia and hypoxia-inducible factors in diabetes and its complications","volume":"64","author":"Catrina","year":"2021","journal-title":"Diabetologia"},{"key":"B32","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.neuro.2012.01.010","article-title":"Industrial toxicants and Parkinson's disease","volume":"33","author":"Caudle","year":"2012","journal-title":"Neurotoxicology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41593-020-0589-7","article-title":"Gut-seeded alpha-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice","volume":"23","author":"Challis","year":"2020","journal-title":"Nat. Neurosci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e0182834","DOI":"10.1371\/journal.pone.0182834","article-title":"Long-term exposure to air pollution and the incidence of Parkinson's disease: a nested case-control study","volume":"12","author":"Chen","year":"2017","journal-title":"PLoS ONE"},{"key":"B35","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.expneurol.2014.02.022","article-title":"\u03b4-Opioid receptor activation reduces \u03b1-synuclein overexpression and oligomer formation induced by MPP(+) and\/or hypoxia","volume":"255","author":"Chen","year":"2014","journal-title":"Exp. Neurol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3463","DOI":"10.1007\/s12035-018-1316-1","article-title":"\u03b4-opioid receptor activation attenuates the oligomer formation induced by hypoxia and\/or \u03b1-synuclein overexpression\/mutation through dual signaling pathways","volume":"56","author":"Chen","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1159\/000064954","article-title":"Parkinsonism after carbon monoxide poisoning","volume":"48","author":"Choi","year":"2002","journal-title":"Eur. Neurol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1289\/ehp.9102","article-title":"Whole-body lifetime occupational lead exposure and risk of Parkinson's disease","volume":"114","author":"Coon","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"B39","doi-asserted-by":"publisher","first-page":"5611","DOI":"10.3390\/ijms21165611","article-title":"Hypoxia and HIF signaling: one axis with divergent effects","volume":"21","author":"Corrado","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"6809","DOI":"10.2174\/1381612811319380013","article-title":"Defective HIF signaling pathway and brain response to hypoxia in neurodegenerative diseases: not an \u201ciffy\u201d question!","volume":"19","author":"Correia","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"B41","doi-asserted-by":"publisher","first-page":"107523","DOI":"10.1016\/j.pharmthera.2020.107523","article-title":"Effects of air pollution on the nervous system and its possible role in neurodevelopmental and neurodegenerative disorders","volume":"210","author":"Costa","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"B42","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40035-017-0088-2","article-title":"Pathological correlations between traumatic brain injury and chronic neurodegenerative diseases","volume":"6","author":"Cruz-Haces","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"B43","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s00702-019-02138-1","article-title":"Conservative iron chelation for neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis","volume":"127","author":"Devos","year":"2020","journal-title":"J. Neural Transm."},{"key":"B44","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.micinf.2016.11.003","article-title":"Hypoxia and HIF-1 activation in bacterial infections","volume":"19","author":"Devraj","year":"2017","journal-title":"Microbes Infect."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1016\/S0140-6736(87)91361-4","article-title":"Increased nigral iron content in postmortem parkinsonian brain","volume":"2","author":"Dexter","year":"1987","journal-title":"Lancet"},{"key":"B46","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/S1474-4422(18)30295-3","article-title":"Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"17","author":"Dorsey","year":"","journal-title":"Lancet Neurol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The emerging evidence of the Parkinson pandemic","volume":"8","author":"Dorsey","year":"","journal-title":"J. Parkinsons. Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.neubiorev.2019.06.018","article-title":"Gene-by-environment interactions in Alzheimer's disease and Parkinson's disease","volume":"103","author":"Dunn","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1081\/CLT-120016955","article-title":"Severe propanil [N-(3,4-dichlorophenyl) propanamide] pesticide self-poisoning","volume":"40","author":"Eddleston","year":"2002","journal-title":"J. Toxicol. Clin. Toxicol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.neurol.2015.09.012","article-title":"Epidemiology of Parkinson's disease","volume":"172","author":"Elbaz","year":"2016","journal-title":"Rev. Neurol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1002\/bdr2.1142","article-title":"Hypoxia: from placental development to fetal programming","volume":"109","author":"Fajersztajn","year":"2017","journal-title":"Birth Defects Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1002\/jbmr.3564","article-title":"The spectrum of fundamental basic science discoveries contributing to organismal aging","volume":"33","author":"Farr","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s00726-019-02759-6","article-title":"Up-regulation of HIF-1\u03b1 is associated with neuroprotective effects of agmatine against rotenone-induced toxicity in differentiated SH-SY5Y cells","volume":"52","author":"Ferlazzo","year":"2020","journal-title":"Amino Acids"},{"key":"B54","doi-asserted-by":"publisher","first-page":"949048","DOI":"10.1155\/2012\/949048","article-title":"Toxic effects of mercury on the cardiovascular and central nervous systems","volume":"2012","author":"Fernandes Azevedo","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/ncb748","article-title":"alpha-Synuclein is phosphorylated in synucleinopathy lesions","volume":"4","author":"Fujiwara","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.sbi.2017.09.004","article-title":"Order and disorder in the physiological membrane binding of \u03b1-synuclein","volume":"48","author":"Fusco","year":"2018","journal-title":"Curr. Opin. Struct. Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/S1388-2457(03)00258-X","article-title":"The neurophysiology of brain injury","volume":"115","author":"Gaetz","year":"2004","journal-title":"Clin. Neurophysiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1002\/glia.24149","article-title":"Neurodegeneration and neuroinflammation are linked, but independent of alpha-synuclein inclusions, in a seeding\/spreading mouse model of Parkinson's disease","volume":"70","author":"Garcia","year":"2022","journal-title":"Glia"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e1771","DOI":"10.1212\/WNL.0000000000005522","article-title":"Mild TBI and risk of Parkinson disease: a chronic effects of neurotrauma consortium study","volume":"90","author":"Gardner","year":"2018","journal-title":"Neurology"},{"key":"B60","first-page":"75","article-title":"Epidemiology of mild traumatic brain injury and neurodegenerative disease","volume-title":"Mol. Cell. Neurosci.","author":"Gardner","year":"2015"},{"key":"B61","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.tins.2010.04.003","article-title":"The propagation of prion-like protein inclusions in neurodegenerative diseases","volume":"33","author":"Goedert","year":"2010","journal-title":"Trends Neurosci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1002\/ana.20882","article-title":"Head injury and Parkinson's disease risk in twins","volume":"60","author":"Goldman","year":"2006","journal-title":"Ann. Neurol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1212\/WNL.48.3.650","article-title":"Occupational exposures to metals as risk factors for Parkinson's disease","volume":"48","author":"Gorell","year":"1997","journal-title":"Neurology"},{"key":"B64","first-page":"239","article-title":"Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson's disease","volume":"20","author":"Gorell","year":"1999","journal-title":"Neurotoxicology"},{"key":"B65","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.pneurobio.2016.06.006","article-title":"Mitochondrial function in hypoxic ischemic injury and influence of aging","volume":"157","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/nrneurol.2015.100","article-title":"Is early-life iron exposure critical in neurodegeneration?","volume":"11","author":"Hare","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1093\/toxsci\/kfu247","article-title":"\u03b1-Synuclein protects against manganese neurotoxic insult during the early stages of exposure in a dopaminergic cell model of Parkinson's disease","volume":"143","author":"Harischandra","year":"2015","journal-title":"Toxicol. Sci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"49071","DOI":"10.1074\/jbc.M208046200","article-title":"Phosphorylated alpha-synuclein is ubiquitinated in alpha-synucleinopathy lesions","volume":"277","author":"Hasegawa","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B69","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/0304-3940(85)90580-4","article-title":"Dopaminergic toxicity of rotenone and the 1-methyl-4-phenylpyridinium ion after their stereotaxic administration to rats: implication for the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity","volume":"62","author":"Heikkila","year":"1985","journal-title":"Neurosci. Lett."},{"key":"B70","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1007\/s00401-014-1343-6","article-title":"Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats","volume":"128","author":"Holmqvist","year":"2014","journal-title":"Acta Neuropathol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1515\/REVEH.2000.15.3.289","article-title":"Anthropogenic emissions of carbon monoxide","volume":"15","author":"Horner","year":"2000","journal-title":"Rev. Environ. Health"},{"key":"B72","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.envres.2018.10.008","article-title":"Association between ambient air pollution and Parkinson's disease: Systematic review and meta-analysis","volume":"168","author":"Hu","year":"2019","journal-title":"Environ. Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1021\/pr060209x","article-title":"Proteomic analysis of hypoxia\/ischemia-induced alteration of cortical development and dopamine neurotransmission in neonatal rat","volume":"5","author":"Hu","year":"2006","journal-title":"J. Proteome Res."},{"key":"B75","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1212\/WNL.0000000000004057","article-title":"Intake of dairy foods and risk of Parkinson disease","volume":"89","author":"Hughes","year":"2017","journal-title":"Neurology"},{"key":"B76","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1177\/1933719114556486","article-title":"Smoking and preterm birth","volume":"22","author":"Ion","year":"2015","journal-title":"Reprod. Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"569","DOI":"10.3233\/JPD-160835","article-title":"Reduction of immunoreactivity against the C-terminal region of the intracellular \u03b1-synuclein by exogenous \u03b1-synuclein aggregates: possibility of conformational changes","volume":"6","author":"Izumi","year":"2016","journal-title":"J. Parkinsons. Dis."},{"key":"B78","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S1474-4422(18)30415-0","article-title":"Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"James","year":"2019","journal-title":"Lancet Neurol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1001\/jamaneurol.2021.1335","article-title":"Association of NO2 and other air pollution exposures with the risk of Parkinson disease","volume":"78","author":"Jo","year":"2021","journal-title":"JAMA Neurol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"105028","DOI":"10.1016\/j.nbd.2020.105028","article-title":"Microglia and astrocyte dysfunction in parkinson's disease","volume":"144","author":"Kam","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"B81","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.neuro.2004.07.010","article-title":"Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis","volume":"26","author":"Kanthasamy","year":"2005","journal-title":"Neurotoxicology"},{"key":"B82","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3389\/fcvm.2018.00018","article-title":"Vascular senescence in cardiovascular and metabolic diseases","volume":"5","author":"Katsuumi","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1002\/mds.25132","article-title":"Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease","volume":"27","author":"Kilarski","year":"2012","journal-title":"Mov. Disord."},{"key":"B84","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.neuron.2019.05.035","article-title":"Transneuronal propagation of pathologic alpha-synuclein from the gut to the brain models Parkinson's disease","volume":"103","author":"Kim","year":"2019","journal-title":"Neuron"},{"key":"B85","doi-asserted-by":"publisher","first-page":"7055","DOI":"10.1523\/JNEUROSCI.1241-16.2016","article-title":"Poststroke induction of \u03b1-synuclein mediates ischemic brain damage","volume":"36","author":"Kim","year":"2016","journal-title":"J. Neurosci."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1177\/0271678X17694186","article-title":"Mechanisms of Parkinson's disease-related proteins in mediating secondary brain damage after cerebral ischemia","volume":"37","author":"Kim","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B87","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s12017-019-08539-5","article-title":"Chronic mild gut inflammation accelerates brain neuropathology and motor dysfunction in \u03b1-synuclein mutant mice","volume":"21","author":"Kishimoto","year":"2019","journal-title":"Neuromol. Med."},{"key":"B88","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1002\/acn3.732","article-title":"Cardiovascular risk factors and Parkinson's disease in 500,000 Chinese adults","volume":"6","author":"Kizza","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"a008888","DOI":"10.1101\/cshperspect.a008888","article-title":"Genetics of Parkinson's disease","volume":"2","author":"Klein","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B90","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1002\/mds.28411","article-title":"Genetic and environmental factors in Parkinson's disease converge on immune function and inflammation","volume":"36","author":"Kline","year":"2021","journal-title":"Mov. Disord."},{"key":"B91","doi-asserted-by":"publisher","first-page":"3390","DOI":"10.1073\/pnas.0810169106","article-title":"Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation","volume":"106","author":"Kr\u00fcger","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B92","doi-asserted-by":"publisher","first-page":"43","DOI":"10.4103\/bc.bc_5_19","article-title":"Therapeutic hypothermia: applications in adults with acute ischemic stroke","volume":"5","author":"Kuczynski","year":"2019","journal-title":"Brain Circ."},{"key":"B93","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/nan.12644","article-title":"Peripheral inflammation exacerbates \u03b1-synuclein toxicity and neuropathology in Parkinson's models","volume":"47","author":"La Vitola","year":"2021","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1590\/S0104-56872005000300014","article-title":"[Ototoxic effects of carbon monoxide exposure: a review","volume":"17","author":"Lacerda","year":"2005","journal-title":"Pro Fono"},{"key":"B95","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.3233\/JPD-179006","article-title":"The MPTP story","volume":"7","author":"Langston","year":"2017","journal-title":"J. Parkinsons. Dis."},{"key":"B96","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1126\/science.6823561","article-title":"Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis","volume":"219","author":"Langston","year":"1983","journal-title":"Science"},{"key":"B97","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1136\/gut.2008.162503","article-title":"Pathological lesions in colonic biopsies during Parkinson's disease","volume":"57","author":"Lebouvier","year":"2008","journal-title":"Gut"},{"key":"B98","doi-asserted-by":"publisher","first-page":"29065","DOI":"10.1074\/jbc.M109.000638","article-title":"Inhibition of prolyl hydroxylase protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity: model for the potential involvement of the hypoxia-inducible factor pathway in Parkinson disease","volume":"284","author":"Lee","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B99","doi-asserted-by":"publisher","first-page":"723","DOI":"10.3390\/biology10080723","article-title":"Hypoxia signaling in Parkinson's disease: there is use in asking \u201cwhat HIF?\u201d","volume":"10","author":"Lest\u00f3n Pinilla","year":"2021","journal-title":"Biology"},{"key":"B100","doi-asserted-by":"publisher","first-page":"406","DOI":"10.3969\/j.issn.1004-5619.2016.06.002","article-title":"Relationship between the expression of \u03b1-syn and neuronal apoptosis in brain cortex of acute alcoholism rats","volume":"32","author":"Li","year":"2016","journal-title":"Fa Yi Xue Za Zhi"},{"key":"B101","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/nm1746","article-title":"Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation","volume":"14","author":"Li","year":"2008","journal-title":"Nat. Med."},{"key":"B102","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1186\/s13046-020-01733-5","article-title":"Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation","volume":"39","author":"Li","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B103","doi-asserted-by":"publisher","first-page":"145","DOI":"10.4103\/bc.bc_11_18","article-title":"Current progress in searching for clinically useful biomarkers of blood-brain barrier damage following cerebral ischemia","volume":"4","author":"Li","year":"2018","journal-title":"Brain Circ."},{"key":"B104","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3389\/fnagi.2018.00121","article-title":"Therapeutic potential of a prolyl hydroxylase inhibitor FG-4592 for Parkinson's diseases in vitro and in vivo: regulation of redox biology and mitochondrial function","volume":"10","author":"Li","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"B105","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.bbrc.2017.01.061","article-title":"PINK1 alleviates myocardial hypoxia-reoxygenation injury by ameliorating mitochondrial dysfunction","volume":"484","author":"Li","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B106","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1080\/17435390.2021.1917716","article-title":"MiR-939-5p suppresses PM(2.5)-induced endothelial injury via targeting HIF-1\u03b1 in HAECs","volume":"15","author":"Liang","year":"2021","journal-title":"Nanotoxicology"},{"key":"B107","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1097\/WNR.0000000000000356","article-title":"Hypoxia-inducible factor-1\u03b1 upregulates tyrosine hydroxylase and dopamine transporter by nuclear receptor ERR\u03b3 in SH-SY5Y cells","volume":"26","author":"Lim","year":"2015","journal-title":"Neuroreport"},{"key":"B108","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1097\/MIB.0000000000000735","article-title":"Association between Parkinson's disease and inflammatory bowel disease: a Nationwide Taiwanese Retrospective Cohort Study","volume":"22","author":"Lin","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"B109","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41380-021-01233-8","article-title":"Deubiquitinating enzymes (DUBs): decipher underlying basis of neurodegenerative diseases","volume":"27","author":"Liu","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"B110","doi-asserted-by":"publisher","first-page":"712","DOI":"10.3390\/cells8070712","article-title":"Mitophagy in Parkinson's disease: from pathogenesis to treatment","volume":"8","author":"Liu","year":"2019","journal-title":"Cells"},{"key":"B111","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.envpol.2017.10.121","article-title":"Diesel exhaust inhalation exposure induces pulmonary arterial hypertension in mice","volume":"237","author":"Liu","year":"2018","journal-title":"Environ. Pollut."},{"key":"B112","doi-asserted-by":"publisher","first-page":"774","DOI":"10.3389\/fphys.2020.00774","article-title":"Novel therapeutic targets for hypoxia-related cardiovascular diseases: the role of HIF-1","volume":"11","author":"Liu","year":"2020","journal-title":"Front. Physiol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s40478-022-01327-6","article-title":"Ischemic stroke causes Parkinson's disease-like pathology and symptoms in transgenic mice overexpressing alpha-synuclein","volume":"10","author":"Lohmann","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"B114","doi-asserted-by":"publisher","first-page":"141","DOI":"10.3390\/ijms20010141","article-title":"Living in promiscuity: the multiple partners of alpha-synuclein at the synapse in physiology and pathology","volume":"20","author":"Longhena","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B115","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"B116","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/978-981-15-4272-5_2","article-title":"Autophagy and Parkinson's disease","volume":"1207","author":"Lu","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/j.jocn.2013.12.016","article-title":"Sex differences in Parkinson's disease","volume":"21","author":"Lubomski","year":"2014","journal-title":"J. Clin. Neurosci."},{"key":"B118","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1084\/jem.20112457","article-title":"Intracerebral inoculation of pathological \u03b1-synuclein initiates a rapidly progressive neurodegenerative \u03b1-synucleinopathy in mice","volume":"209","author":"Luk","year":"2012","journal-title":"J. Exp. Med."},{"key":"B119","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1097\/JOM.0000000000000089","article-title":"Short-term effects of air pollution on oxygen saturation in a cohort of senior adults in Steubenville, Ohio","volume":"56","author":"Luttmann-Gibson","year":"2014","journal-title":"J. Occup. Environ. Med."},{"key":"B120","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41419-018-0297-3","article-title":"Norisoboldine, a natural AhR agonist, promotes Treg differentiation and attenuates colitis via targeting glycolysis and subsequent NAD(+)\/SIRT1\/SUV39H1\/H3K9me3 signaling pathway","volume":"9","author":"Lv","year":"2018","journal-title":"Cell Death Dis."},{"key":"B121","doi-asserted-by":"publisher","first-page":"40732","DOI":"10.1074\/jbc.M110.141952","article-title":"Phosphorylated alpha-synuclein at Ser-129 is targeted to the proteasome pathway in a ubiquitin-independent manner","volume":"285","author":"Machiya","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B122","doi-asserted-by":"publisher","first-page":"6454","DOI":"10.3390\/ijms21186454","article-title":"Neuroinflammatory mechanisms in ischemic stroke: focus on cardioembolic stroke, background, and therapeutic approaches","volume":"21","author":"Maida","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B123","article-title":"Pathological \u03b1-synuclein transmission initiated by binding lymphocyte-activation gene 3","volume-title":"Science","author":"Mao","year":"2016"},{"key":"B124","doi-asserted-by":"publisher","first-page":"8421","DOI":"10.3390\/ijms21228421","article-title":"Neurodegeneration and inflammation-an interesting interplay in Parkinson's Disease","volume":"21","author":"Marogianni","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B125","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1016\/j.bbapap.2019.03.001","article-title":"\u03b1-Synuclein misfolding and aggregation: implications in Parkinson's disease pathogenesis","volume":"1867","author":"Mehra","year":"2019","journal-title":"Biochim. Biophys. Acta Prot. Proteom"},{"key":"B126","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1139\/bcb-2019-0117","article-title":"Protective effect of hydralazine on a cellular model of Parkinson's disease: a possible role of hypoxia-inducible factor (HIF)-1\u03b1","volume":"98","author":"Mehrabani","year":"2020","journal-title":"Biochem. Cell Biol."},{"key":"B127","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s10571-016-0355-2","article-title":"Sirt1: role under the condition of ischemia\/hypoxia","volume":"37","author":"Meng","year":"2017","journal-title":"Cell. Mol. Neurobiol."},{"key":"B128","doi-asserted-by":"publisher","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":"B129","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1016\/j.freeradbiomed.2007.01.015","article-title":"ROS generation in endothelial hypoxia and reoxygenation stimulates MAP kinase signaling and kinase-dependent neutrophil recruitment","volume":"42","author":"Millar","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"B130","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1523\/JNEUROSCI.2482-06.2007","article-title":"Lack of hypoxia-inducible factor-1 alpha impairs midbrain neural precursor cells involving vascular endothelial growth factor signaling","volume":"27","author":"Milosevic","year":"2007","journal-title":"J. Neurosci."},{"key":"B131","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1038\/s41598-021-81185-9","article-title":"Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration","volume":"11","author":"Muddapu","year":"2021","journal-title":"Sci. Rep."},{"key":"B132","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1002\/mds.28922","article-title":"Air pollution and the risk of Parkinson's disease: a review","volume":"37","author":"Murata","year":"2022","journal-title":"Mov. Disord"},{"key":"B133","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.pnpbp.2015.03.013","article-title":"Drugs of abuse and Parkinson's disease","volume":"64","author":"Mursaleen","year":"2016","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B134","doi-asserted-by":"publisher","first-page":"20710","DOI":"10.1074\/jbc.M110.213538","article-title":"Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein","volume":"286","author":"Nakamura","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B135","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/nrneurol.2009.136","article-title":"Parkinson disease and comorbid cerebrovascular disease","volume":"5","author":"Nanhoe-Mahabier","year":"2009","journal-title":"Nat. Rev. Neurol."},{"key":"B136","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1002\/mds.21317","article-title":"Vitamin D and Parkinson's disease\u2013a hypothesis","volume":"22","author":"Newmark","year":"2007","journal-title":"Mov. Disord."},{"key":"B137","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.tins.2018.11.001","article-title":"Synaptic, mitochondrial, and lysosomal dysfunction in Parkinson's disease","volume":"42","author":"Nguyen","year":"2019","journal-title":"Trends Neurosci."},{"key":"B138","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1016\/j.cub.2015.07.050","article-title":"Elevated mitochondrial bioenergetics and axonal arborization size are key contributors to the vulnerability of dopamine neurons","volume":"25","author":"Pacelli","year":"2015","journal-title":"Curr. Biol."},{"key":"B139","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1515\/reveh-2017-0009","article-title":"Air pollution and Parkinson's disease - evidence and future directions","volume":"32","author":"Palacios","year":"2017","journal-title":"Rev. Environ. Health"},{"key":"B140","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s40035-019-0165-9","article-title":"The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson's disease","volume":"8","author":"Pang","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"B141","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.3390\/jcm8081191","article-title":"Patients with inflammatory bowel disease are at an increased risk of Parkinson's disease: A South Korean Nationwide Population-Based Study","volume":"8","author":"Park","year":"2019","journal-title":"J. Clin. Med."},{"key":"B142","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1001\/jamaneurol.2018.0605","article-title":"Anti-tumor necrosis factor therapy and incidence of Parkinson disease among patients with inflammatory bowel disease","volume":"75","author":"Peter","year":"2018","journal-title":"JAMA Neurol."},{"key":"B143","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1212\/WNL.0b013e318294b3c8","article-title":"Exposure to pesticides or solvents and risk of Parkinson disease","volume":"80","author":"Pezzoli","year":"2013","journal-title":"Neurology"},{"key":"B144","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s10048-011-0292-7","article-title":"Genetic variability in SNCA and Parkinson's disease","volume":"12","author":"Pihlstr\u00f8m","year":"2011","journal-title":"Neurogenetics"},{"key":"B145","doi-asserted-by":"publisher","first-page":"4405","DOI":"10.3390\/ijms22094405","article-title":"Neuroinflammation in post-ischemic neurodegeneration of the brain: friend, foe, or both?","volume":"22","author":"Pluta","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B146","doi-asserted-by":"publisher","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B147","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the alpha-synuclein gene identified in families with Parkinson's disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"B148","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1093\/ije\/dyx225","article-title":"Pesticide use in agriculture and Parkinson's disease in the AGRICAN cohort study","volume":"47","author":"Pouchieu","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"B149","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s00401-018-1943-7","article-title":"Enteric alpha-synuclein expression is increased in Crohn's disease","volume":"137","author":"Prigent","year":"2019","journal-title":"Acta Neuropathol."},{"key":"B150","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1002\/mds.25945","article-title":"The prevalence of Parkinson's disease: a systematic review and meta-analysis","volume":"29","author":"Pringsheim","year":"2014","journal-title":"Mov. Disord."},{"key":"B151","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1083\/jcb.201509003","article-title":"PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy","volume":"213","author":"Pryde","year":"2016","journal-title":"J. Cell Biol."},{"key":"B152","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.4103\/1673-5374.262599","article-title":"Relationship between high dietary fat intake and Parkinson's disease risk: a meta-analysis","volume":"14","author":"Qu","year":"2019","journal-title":"Neural Regen. Res."},{"key":"B153","doi-asserted-by":"publisher","first-page":"113","DOI":"10.2147\/JIR.S196552","article-title":"Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates","volume":"12","author":"Resnikoff","year":"2019","journal-title":"J. Inflamm. Res."},{"key":"B154","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.bbi.2012.11.017","article-title":"Loss of substance P and inflammation precede delayed neurodegeneration in the substantia nigra after cerebral ischemia","volume":"29","author":"Rodriguez-Grande","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"B155","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s11910-017-0737-y","article-title":"\u03b1-synuclein and Parkinsonism: updates and future perspectives","volume":"17","author":"Rosborough","year":"2017","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"B156","doi-asserted-by":"publisher","first-page":"9608","DOI":"10.3390\/ijms22179608","article-title":"Novel approaches used to examine and control neurogenesis in Parkinson's disease","volume":"22","author":"Salmina","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B157","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1002\/mds.25988","article-title":"In vivo gastric detection of \u03b1-synuclein inclusions in Parkinson's disease","volume":"30","author":"S\u00e1nchez-Ferro","year":"2015","journal-title":"Mov. Disord."},{"key":"B158","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1093\/jnen\/nly024","article-title":"Increased oxidative stress exacerbates \u03b1-synuclein aggregation in vivo","volume":"77","author":"Scudamore","year":"2018","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B159","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/nrc1187","article-title":"Targeting HIF-1 for cancer therapy","volume":"3","author":"Semenza","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"B160","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/0-306-46825-5_12","article-title":"Hypoxia, HIF-1, and the pathophysiology of common human diseases","volume":"475","author":"Semenza","year":"2000","journal-title":"Adv. Exp. Med. Biol."},{"key":"B161","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1002\/mds.23838","article-title":"Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease","volume":"27","author":"Shannon","year":"2012","journal-title":"Mov. Disord."},{"key":"B162","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.brainres.2014.09.046","article-title":"\u03b1-Synuclein amino terminus regulates mitochondrial membrane permeability","volume":"1591","author":"Shen","year":"2014","journal-title":"Brain Res."},{"key":"B163","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1111\/crj.12718","article-title":"Changes in inflammatory mediators as a result of intermittent hypoxia in obstructive sleep apnea syndrome","volume":"12","author":"Sozer","year":"2018","journal-title":"Clin. Respir. J."},{"key":"B164","doi-asserted-by":"publisher","first-page":"6469","DOI":"10.1073\/pnas.95.11.6469","article-title":"alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies","volume":"95","author":"Spillantini","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B165","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"B166","doi-asserted-by":"publisher","first-page":"736978","DOI":"10.3389\/fmed.2021.736978","article-title":"Alpha-synuclein aggregation in Parkinson's disease","volume":"8","author":"Srinivasan","year":"2021","journal-title":"Front. Med."},{"key":"B167","doi-asserted-by":"publisher","first-page":"18412","DOI":"10.1038\/s41598-020-75361-6","article-title":"Fast kinetics of environmentally induced \u03b1-synuclein aggregation mediated by structural alteration in NAC region and result in structure dependent cytotoxicity","volume":"10","author":"Srivastava","year":"2020","journal-title":"Sci. Rep."},{"key":"B168","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.2741\/4657","article-title":"Survival of the fittest: VO(2)max, a key predictor of longevity?","volume":"23","author":"Strasser","year":"2018","journal-title":"Front. Biosci."},{"key":"B169","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1002\/acn3.756","article-title":"Plasma \u03b1-synuclein levels are increased in patients with obstructive sleep apnea syndrome","volume":"6","author":"Sun","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B170","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/ana.24448","article-title":"Vagotomy and subsequent risk of Parkinson's disease","volume":"78","author":"Svensson","year":"2015","journal-title":"Ann. Neurol."},{"key":"B171","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1016\/j.celrep.2015.08.001","article-title":"VPS35 deficiency or mutation causes dopaminergic neuronal loss by impairing mitochondrial fusion and function","volume":"12","author":"Tang","year":"2015","journal-title":"Cell Rep."},{"key":"B172","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/978-1-4939-3816-2_26","article-title":"Experimental models combining traumatic brain injury and hypoxia","volume":"1462","author":"Thelin","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"B173","doi-asserted-by":"publisher","first-page":"597","DOI":"10.3233\/JAD-190015","article-title":"Air pollution, stress, and allostatic load: linking systemic and central nervous system impacts","volume":"69","author":"Thomson","year":"2019","journal-title":"J. Alzheimers. Dis."},{"key":"B174","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S1474-4422(21)00030-2","article-title":"Challenges in the diagnosis of Parkinson's disease","volume":"20","author":"Tolosa","year":"2021","journal-title":"Lancet Neurol."},{"key":"B175","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12995-021-00309-z","article-title":"Mortality from Parkinson's disease and other causes among a workforce manufacturing paraquat: an updated retrospective cohort study","volume":"16","author":"Tomenson","year":"2021","journal-title":"J. Occup. Med. Toxicol."},{"key":"B176","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1021\/acschemneuro.8b00407","article-title":"Interaction of \u03b1-synuclein with ATP synthase: switching role from physiological to pathological","volume":"10","author":"Tripathi","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"B177","doi-asserted-by":"publisher","first-page":"e13522","DOI":"10.1111\/acel.13522","article-title":"\u03b1-synuclein suppresses microglial autophagy and promotes neurodegeneration in a mouse model of Parkinson's disease","volume":"20","author":"Tu","year":"2021","journal-title":"Aging Cell"},{"key":"B178","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.toxrep.2021.03.009","article-title":"Metal elements and pesticides as risk factors for Parkinson's disease - A review","volume":"8","author":"Ullah","year":"2021","journal-title":"Toxicol. Rep."},{"key":"B179","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/jcbfm.2010.170","article-title":"Alpha-synuclein aggregation induced by brief ischemia negatively impacts neuronal survival in vivo: a study in [A30P]alpha-synuclein transgenic mouse","volume":"31","author":"Unal-Cevik","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B180","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/nrgastro.2017.101","article-title":"Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD","volume":"14","author":"Van Welden","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B181","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1002\/mds.26566","article-title":"Glycation in Parkinson's disease and Alzheimer's disease","volume":"31","author":"Vicente Miranda","year":"2016","journal-title":"Mov. Disord."},{"key":"B182","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/BF00294234","article-title":"Parkinson's disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system","volume":"79","author":"Wakabayashi","year":"1990","journal-title":"Acta Neuropathol."},{"key":"B183","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nm.3983","article-title":"Parkinson's disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes","volume":"22","author":"Wang","year":"2016","journal-title":"Nat. Med."},{"key":"B184","doi-asserted-by":"publisher","first-page":"H2137","DOI":"10.1152\/ajpheart.00149.2015","article-title":"At high cardiac output, diesel exhaust exposure increases pulmonary vascular resistance and decreases distensibility of pulmonary resistive vessels","volume":"309","author":"Wauters","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B185","doi-asserted-by":"publisher","first-page":"616083","DOI":"10.3389\/fgene.2020.616083","article-title":"The function of the metals in regulating epigenetics during Parkinson's disease","volume":"11","author":"Wei","year":"2020","journal-title":"Front. Genet."},{"key":"B186","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/ibd\/izy190","article-title":"Inflammatory bowel disease and Parkinson's disease: A Nationwide Swedish Cohort Study","volume":"25","author":"Weimers","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"B187","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1289\/ehp.1002339","article-title":"Association of cumulative lead exposure with Parkinson's disease","volume":"118","author":"Weisskopf","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"B188","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/S1474-4422(17)30279-X","article-title":"The chronic and evolving neurological consequences of traumatic brain injury","volume":"16","author":"Wilson","year":"2017","journal-title":"Lancet Neurol."},{"key":"B189","doi-asserted-by":"publisher","first-page":"4194","DOI":"10.1073\/pnas.1100976108","article-title":"In vivo demonstration that alpha-synuclein oligomers are toxic","volume":"108","author":"Winner","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B190","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1159\/000275491","article-title":"Geographic and ethnic variation in Parkinson disease: a population-based study of US Medicare beneficiaries","volume":"34","author":"Wright Willis","year":"2010","journal-title":"Neuroepidemiology"},{"key":"B191","doi-asserted-by":"publisher","first-page":"149132","DOI":"10.1016\/j.scitotenv.2021.149132","article-title":"Particle-bound PAHs induced glucose metabolism disorders through HIF-1 pathway","volume":"797","author":"Wu","year":"2021","journal-title":"Sci. Total Environ."},{"key":"B192","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.parkreldis.2010.02.007","article-title":"Iron and reactive oxygen species activity in parkinsonian substantia nigra","volume":"16","author":"Wypijewska","year":"2010","journal-title":"Parkinsonism Relat. Disord."},{"key":"B193","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/nature20411","article-title":"Ageing, neurodegeneration and brain rejuvenation","volume":"539","author":"Wyss-Coray","year":"2016","journal-title":"Nature"},{"key":"B194","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1007\/s12035-018-1206-6","article-title":"Impaired mitophagy and protein acetylation levels in fibroblasts from Parkinson's disease patients","volume":"56","author":"Yakhine-Diop","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B195","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1097\/SHK.0000000000000037","article-title":"Interleukin 6 mediates neuroinflammation and motor coordination deficits after mild traumatic brain injury and brief hypoxia in mice","volume":"40","author":"Yang","year":"2013","journal-title":"Shock"},{"key":"B196","doi-asserted-by":"publisher","first-page":"e96509","DOI":"10.1371\/journal.pone.0096509","article-title":"Hypoxia Induces autophagic cell death through hypoxia-inducible factor 1\u03b1 in microglia","volume":"9","author":"Yang","year":"2014","journal-title":"PLoS ONE"},{"key":"B197","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/ijo.2008.229","article-title":"Emerging role of adipose tissue hypoxia in obesity and insulin resistance","volume":"33","author":"Ye","year":"2009","journal-title":"Int. J. Obes."},{"key":"B198","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0233-3","article-title":"Hypoxia and aging","volume":"51","author":"Yeo","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"B199","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1249\/JSR.0b013e31827ec9e3","article-title":"Chronic traumatic encephalopathy","volume":"12","author":"Yi","year":"2013","journal-title":"Curr. Sports Med. Rep."},{"key":"B200","doi-asserted-by":"publisher","first-page":"792764","DOI":"10.3389\/fncel.2021.792764","article-title":"Reactive astrocytes in central nervous system injury: subgroup and potential therapy","volume":"15","author":"Yu","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"B201","first-page":"263","article-title":"Effect of repeated acute hypoxic treatment on the expression of alpha-synuclein in the mouse brain cortex","volume":"56","author":"Yu","year":"2004","journal-title":"Sheng Li Xue Bao"},{"key":"B202","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1007\/s10072-016-2660-4","article-title":"Parkinson's disease and cerebrovascular disease: is there a link? A neurosonological case-control study","volume":"37","author":"Zambito Marsala","year":"2016","journal-title":"Neurol. Sci."},{"key":"B203","doi-asserted-by":"publisher","first-page":"370","DOI":"10.3389\/fnagi.2018.00370","article-title":"New perspectives on roles of alpha-synuclein in Parkinson's disease","volume":"10","author":"Zhang","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"B204","doi-asserted-by":"publisher","first-page":"e2011196118","DOI":"10.1073\/pnas.2011196118","article-title":"Mechanistic basis for receptor-mediated pathological \u03b1-synuclein fibril cell-to-cell transmission in Parkinson's disease","volume":"118","author":"Zhang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B205","first-page":"1237","article-title":"Cerebral blood flow, cerebral blood volume, oxygen utilization and oxygen extraction fraction: the influence of age","volume":"30","author":"Zhang","year":"2010","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"B206","doi-asserted-by":"publisher","first-page":"4335","DOI":"10.2174\/092986711797200426","article-title":"Hypoxia inducible factor-1 as a target for neurodegenerative diseases","volume":"18","author":"Zhang","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"B207","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s10072-016-2485-1","article-title":"A comparative study of the amount of \u03b1-synuclein in ischemic stroke and Parkinson's disease","volume":"37","author":"Zhao","year":"2016","journal-title":"Neurol. Sci."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.919343\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T05:02:13Z","timestamp":1658811733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.919343\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,26]]},"references-count":207,"alternative-id":["10.3389\/fnagi.2022.919343"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.919343","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,26]]},"article-number":"919343"}}