{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:01:35Z","timestamp":1787504495370,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences (CIFMS)","award":["2021-I2M-1-026"],"award-info":[{"award-number":["2021-I2M-1-026"]}]},{"name":"CAMS Innovation Fund for Medical Sciences (CIFMS)","award":["81773925"],"award-info":[{"award-number":["81773925"]}]},{"name":"CAMS Innovation Fund for Medical Sciences (CIFMS)","award":["7212156"],"award-info":[{"award-number":["7212156"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021-I2M-1-026"],"award-info":[{"award-number":["2021-I2M-1-026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773925"],"award-info":[{"award-number":["81773925"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["7212156"],"award-info":[{"award-number":["7212156"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["2021-I2M-1-026"],"award-info":[{"award-number":["2021-I2M-1-026"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["81773925"],"award-info":[{"award-number":["81773925"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7212156"],"award-info":[{"award-number":["7212156"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Accumulating evidence has shown that Parkinson\u2019s disease (PD) is a systemic disease other than a mere central nervous system (CNS) disorder. One of the most important peripheral symptoms is gastrointestinal dysfunction. The enteric nervous system (ENS) is regarded as an essential gateway to the environment. The discovery of the prion-like behavior of \u03b1-synuclein makes it possible for the neurodegenerative process to start in the ENS and spread via the gut-brain axis to the CNS. We first confirmed that synucleinopathies existed in the stomachs of chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)\/probenecid (MPTP\/p)-induced PD mice, as indicated by the significant increase in abnormal aggregated and nitrated \u03b1-synuclein in the TH-positive neurons and enteric glial cells (EGCs) of the gastric myenteric plexus. Next, we attempted to clarify the mechanisms in single MPTP-injected mice. The stomach naturally possesses high monoamine oxidase-B (MAO-B) activity and low superoxide dismutase (SOD) activity, making the stomach susceptible to MPTP-induced oxidative stress, as indicated by the significant increase in reactive oxygen species (ROS) in the stomach and elevated 4-hydroxynonenal (4-HNE) in the EGCs after MPTP exposure for 3 h. Additionally, stomach synucleinopathies appear before those of the nigrostriatal system, as determined by Western blotting 12 h after MPTP injection. Notably, nitrated \u03b1-synuclein was considerably increased in the EGCs after 3 h and 12 h of MPTP exposure. Taken together, our work demonstrated that the EGCs could be new contributors to synucleinopathies in the stomach. The early-initiated synucleinopathies might further influence neighboring neurons in the myenteric plexus and the CNS. Our results offer a new experimental clue for interpreting the etiology of PD.<\/jats:p>","DOI":"10.3390\/molecules27217414","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T08:15:12Z","timestamp":1667376912000},"page":"7414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Gastric Enteric Glial Cells: A New Contributor to the Synucleinopathies in the MPTP-Induced Parkinsonism Mouse"],"prefix":"10.3390","volume":"27","author":[{"given":"Yang","family":"Heng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Yan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Qing","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National Cancer Center\/National, Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union, Medical College, Beijing 100021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6354-7853","authenticated-orcid":false,"given":"Nai-Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-He","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.amjmed.2019.03.001","article-title":"Parkinson\u2019s Disease and Parkinsonism","volume":"132","author":"Hayes","year":"2019","journal-title":"Am. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1021\/acschemneuro.1c00877","article-title":"Current Progress in the Development of Probes for Targeting alpha-Synuclein Aggregates","volume":"13","author":"Zeng","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.brainres.2018.01.010","article-title":"Parkinson\u2019s disease from the gut","volume":"1693 (Pt B)","author":"Liddle","year":"2018","journal-title":"Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cger.2019.08.002","article-title":"Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology","volume":"36","author":"Simon","year":"2020","journal-title":"Clin. Geriatr. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/nature17891","article-title":"Parkinson\u2019s disease: Guilt by genetic association","volume":"533","author":"Abeliovich","year":"2016","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1055\/s-0037-1601567","article-title":"Genetic Forms of Parkinson\u2019s Disease","volume":"37","author":"Kim","year":"2017","journal-title":"Semin. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1093\/brain\/awt037","article-title":"Prion-like spreading of pathological alpha-synuclein in brain","volume":"136","author":"Nonaka","year":"2013","journal-title":"Brain J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134316","DOI":"10.1016\/j.neulet.2019.134316","article-title":"alpha-Synuclein pathology in Parkinson\u2019s disease and related alpha-synucleinopathies","volume":"709","author":"Henderson","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nrneurol.2016.54","article-title":"Parkinson disease: Peripheral alpha-synuclein deposits\u2014Prodromal markers for Parkinson disease?","volume":"12","author":"Wood","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"a024091","DOI":"10.1101\/cshperspect.a024091","article-title":"Cell Biology and Pathophysiology of alpha-Synuclein","volume":"8","author":"Burre","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s10571-021-01066-7","article-title":"The Gut-Brain Axis: Two Ways Signaling in Parkinson\u2019s Disease","volume":"42","author":"Dogra","year":"2022","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/srep00898","article-title":"Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice","volume":"2","author":"Schwarz","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","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":"ref_14","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/S1474-4422(15)00006-X","article-title":"Targeting alpha-synuclein for treatment of Parkinson\u2019s disease: Mechanistic and therapeutic considerations","volume":"14","author":"Dehay","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ijbiomac.2016.10.021","article-title":"alpha-synuclein aggregation and its modulation","volume":"100","author":"Ghosh","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1021\/acschemneuro.1c00028","article-title":"Effects of alpha-Synuclein-Associated Post-Translational Modifications in Parkinson\u2019s Disease","volume":"12","author":"He","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.bbadis.2011.10.002","article-title":"Alpha-synuclein misfolding and Parkinson\u2019s disease","volume":"1822","author":"Breydo","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41586-019-1808-9","article-title":"Regulation of alpha-synuclein by chaperones in mammalian cells","volume":"577","author":"Burmann","year":"2020","journal-title":"Nature"},{"key":"ref_19","first-page":"S11","article-title":"The MPTP Story","volume":"7","author":"Langston","year":"2017","journal-title":"J. Park. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nprot.2006.342","article-title":"Protocol for the MPTP mouse model of Parkinson\u2019s disease","volume":"2","author":"Przedborski","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.neuroscience.2018.04.008","article-title":"Methylene Blue Ameliorates Olfactory Dysfunction and Motor Deficits in a Chronic MPTP\/Probenecid Mouse Model of Parkinson\u2019s Disease","volume":"380","author":"Biju","year":"2018","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kin, K., Yasuhara, T., Kameda, M., and Date, I. (2019). Animal Models for Parkinson\u2019s Disease Research: Trends in the 2000s. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215402"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.nbd.2017.04.004","article-title":"Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson\u2019s disease","volume":"109","author":"Rocha","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Marogianni, C., Sokratous, M., Dardiotis, E., Hadjigeorgiou, G.M., Bogdanos, D., and Xiromerisiou, G. (2020). Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228421"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"134640","DOI":"10.1016\/j.neulet.2019.134640","article-title":"Alpha-synuclein oligomerization and dopaminergic degeneration occur synchronously in the brain and colon of MPTP-intoxicated parkinsonian monkeys","volume":"716","author":"Li","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1111\/j.1471-4159.2009.06072.x","article-title":"Differences between subacute and chronic MPTP mice models: Investigation of dopaminergic neuronal degeneration and alpha-synuclein inclusions","volume":"109","author":"Gibrat","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7934","DOI":"10.1038\/s41598-021-86917-5","article-title":"The association of enteric neuropathy with gut phenotypes in acute and progressive models of Parkinson\u2019s disease","volume":"11","author":"McQuade","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00401-012-0964-x","article-title":"An antibody with high reactivity for disease-associated alpha-synuclein reveals extensive brain pathology","volume":"124","author":"Kovacs","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.toxlet.2015.12.005","article-title":"Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting alpha-synuclein abnormalities in the substantia nigra","volume":"243","author":"Heng","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.abb.2013.02.009","article-title":"Oxidation and nitration of alpha-synuclein and their implications in neurodegenerative diseases","volume":"533","author":"Chavarria","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ydbio.2012.02.024","article-title":"Arx is required for normal enteroendocrine cell development in mice and humans","volume":"365","author":"Du","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"a016287","DOI":"10.1101\/cshperspect.a016287","article-title":"Inflammasomes","volume":"6","author":"Palm","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1007\/s00018-012-1140-0","article-title":"NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1beta and neuronal toxicity","volume":"69","author":"Bencina","year":"2012","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/jnc.12481","article-title":"Non-motor parkinsonian pathology in aging A53T alpha-synuclein mice is associated with progressive synucleinopathy and altered enzymatic function","volume":"128","author":"Farrell","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11010-012-1400-1","article-title":"Red blood cell lysate modulates the expression of extracellular matrix proteins in dermal fibroblasts","volume":"370","author":"Akbari","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.bbr.2015.07.058","article-title":"Environment-contact administration of rotenone: A new rodent model of Parkinson\u2019s disease","volume":"294","author":"Liu","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.neuro.2015.09.009","article-title":"Protective effects of Forsythia suspense extract with antioxidant and anti-inflammatory properties in a model of rotenone induced neurotoxicity","volume":"52","author":"Zhang","year":"2015","journal-title":"Neurotoxicology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1146\/annurev-biochem-061516-045049","article-title":"Propagation of Protein Aggregation in Neurodegenerative Diseases","volume":"88","author":"Diamond","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1007\/s00401-014-1265-3","article-title":"The oligomer modulator anle138b inhibits disease progression in a Parkinson mouse model even with treatment started after disease onset","volume":"127","author":"Levin","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Candelise, N., Scaricamazza, S., Salvatori, I., Ferri, A., Valle, C., Manganelli, V., Garofalo, T., Sorice, M., and Misasi, R. (2021). Protein Aggregation Landscape in Neurodegenerative Diseases: Clinical Relevance and Future Applications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116016"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41591-021-01382-x","article-title":"Biomarkers for neurodegenerative diseases","volume":"27","author":"Hansson","year":"2021","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1021\/acschemneuro.8b00288","article-title":"Alpha-Synuclein Nitration and Its Implications in Parkinson\u2019s Disease","volume":"10","author":"He","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.nbd.2018.04.008","article-title":"Astrocyte-specific DJ-1 overexpression protects against rotenone-induced neurotoxicity in a rat model of Parkinson\u2019s disease","volume":"115","author":"Rocha","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/jnr.22549","article-title":"Low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine causes inflammatory activation of astrocytes in nuclear factor-kappaB reporter mice prior to loss of dopaminergic neurons","volume":"89","author":"Miller","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neuroscience.2011.10.057","article-title":"Neurotoxin-based models of Parkinson\u2019s disease","volume":"211","author":"Bove","year":"2012","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neulet.2013.10.049","article-title":"Remodeling of the dendritic structure of the striatal medium spiny neurons accompanies behavioral recovery in a mouse model of Parkinson\u2019s disease","volume":"557","author":"Kim","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_47","first-page":"4883","article-title":"(-)-Epigallocatechin-3-gallate modulates peripheral immunity in the MPTP-induced mouse model of Parkinson\u2019s disease","volume":"17","author":"Zhou","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1600-0773.1990.tb00743.x","article-title":"Distribution of 1-(3H)-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (3H-MPTP) in the frog: Uptake in neuromelanin","volume":"66","author":"Sokolowski","year":"1990","journal-title":"Pharmacol. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/aps.2017.49","article-title":"Reassessment of subacute MPTP-treated mice as animal model of Parkinson\u2019s disease","volume":"38","author":"Zhang","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1080\/17425255.2019.1607292","article-title":"Pharmacokinetics of monoamine oxidase B inhibitors in Parkinson\u2019s disease: Current status","volume":"15","author":"Muller","year":"2019","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1002\/med.21561","article-title":"Monoamine oxidase-B inhibitors as potential neurotherapeutic agents: An overview and update","volume":"39","author":"Tripathi","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2051-5960-1-2","article-title":"The prion hypothesis in Parkinson\u2019s disease: Braak to the future","volume":"1","author":"Visanji","year":"2013","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00441-004-0956-9","article-title":"Stages in the development of Parkinson\u2019s disease-related pathology","volume":"318","author":"Braak","year":"2004","journal-title":"Cell Tissue Res."},{"key":"ref_54","doi-asserted-by":"crossref","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\u2019s Disease","volume":"103","author":"Kim","year":"2019","journal-title":"Neuron"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"317","DOI":"10.5114\/fn.2019.89857","article-title":"Rotenone: From modelling to implication in Parkinson\u2019s disease","volume":"57","author":"Radad","year":"2019","journal-title":"Folia Neuropathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41593-019-0556-3","article-title":"Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain","volume":"23","author":"Graves","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7374","DOI":"10.1002\/anie.201600277","article-title":"Toxic dopamine metabolite DOPAL forms an unexpected dicatechol pyrrole adduct with lysines of alpha-synuclein","volume":"55","author":"DuMond","year":"2016","journal-title":"Angew. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00401-007-0303-9","article-title":"Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine","volume":"115","author":"Burke","year":"2008","journal-title":"Acta Neuropathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"40699","DOI":"10.1038\/srep40699","article-title":"DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function","volume":"7","author":"Plotegher","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jns.2018.07.011","article-title":"1-Methyl-4-phenyl-1,2,3,6 tetrahydropyridine\/probenecid impairs intestinal motility and olfaction in the early stages of Parkinson\u2019s disease in mice","volume":"392","author":"Choi","year":"2018","journal-title":"J. Neurol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13195-014-0073-2","article-title":"Alpha-synuclein biology in Lewy body diseases","volume":"6","author":"Kim","year":"2014","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/jnc.12226","article-title":"Oxidative and nitrative alpha-synuclein modifications and proteostatic stress: Implications for disease mechanisms and interventions in synucleinopathies","volume":"125","author":"Schildknecht","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1172\/JCI127330","article-title":"Oxidative stress in vagal neurons promotes parkinsonian pathology and intercellular alpha-synuclein transfer","volume":"129","author":"Musgrove","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e315","DOI":"10.1038\/cddis.2012.50","article-title":"Increased alpha-synuclein phosphorylation and nitration in the aging primate substantia nigra","volume":"3","author":"McCormack","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1266\/ggs.18-00036","article-title":"Transcriptome sequencing in a 6-hydroxydopamine rat model of Parkinson\u2019s disease","volume":"94","author":"Li","year":"2019","journal-title":"Genes Genet. Syst."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/apha.12229","article-title":"The role of the vagal pathway and gastric dopamine in the gastroparesis of rats after a 6-hydroxydopamine microinjection in the substantia nigra","volume":"211","author":"Zheng","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1053\/j.gastro.2014.09.040","article-title":"Enteric glial cells: Recent developments and future directions","volume":"147","author":"Neunlist","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1172\/JCI76303","article-title":"Emerging roles for enteric glia in gastrointestinal disorders","volume":"125","author":"Sharkey","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrneurol.2015.197","article-title":"Pathogenesis of Parkinson disease\u2014The gut\u2014Brain axis and environmental factors","volume":"11","author":"Klingelhoefer","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1113\/JP271021","article-title":"Enteric glia: The most alimentary of all glia","volume":"595","author":"Grubisic","year":"2016","journal-title":"J. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1053\/j.gastro.2013.10.061","article-title":"Ca2+ responses in enteric glia are mediated by connexin-43 hemichannels and modulate colonic transit in mice","volume":"146","author":"McClain","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.jcmgh.2015.08.004","article-title":"Agonist-evoked Ca signaling in enteric glia drives neural programs that regulate intestinal motility in mice","volume":"1","author":"McClain","year":"2015","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/cdd.2012.142","article-title":"The Ca2+\/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to alpha-synuclein toxicity in Parkinson\u2019s disease models","volume":"20","author":"Buttner","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.mcn.2010.12.004","article-title":"Raised calcium promotes alpha-synuclein aggregate formation","volume":"46","author":"Nath","year":"2011","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1097\/WNR.0b013e3280115185","article-title":"Alpha-synuclein potentiates Ca2+ influx through voltage-dependent Ca2+ channels","volume":"17","author":"Adamczyk","year":"2006","journal-title":"Neuroreport"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"795","DOI":"10.3390\/biom4030795","article-title":"Interactions between calcium and alpha-synuclein in neurodegeneration","volume":"4","author":"Goodwin","year":"2014","journal-title":"Biomolecules"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/21\/7414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:08:41Z","timestamp":1760144921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/21\/7414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":77,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["molecules27217414"],"URL":"https:\/\/doi.org\/10.3390\/molecules27217414","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]}}}