{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:24:33Z","timestamp":1791519873240,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005088","name":"Beijing Municipal Health Commission","doi-asserted-by":"publisher","award":["303\u201001\u2010005\u20100019"],"award-info":[{"award-number":["303\u201001\u2010005\u20100019"]}],"id":[{"id":"10.13039\/501100005088","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["Z211100002121038"],"award-info":[{"award-number":["Z211100002121038"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100925"],"award-info":[{"award-number":["32100925"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82027802"],"award-info":[{"award-number":["82027802"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>The etiology of Parkinson's disease (PD) is complex and the mechanism is unclear. It has become a top priority to find common factors that induce and affect PD pathology. We explored the key role of hypoxia in promoting the pathological propagation of \u03b1\u2010synuclein (\u03b1\u2010syn) and the progression of PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed PD modeling by conducting intracranial stereotaxic surgery in the unilateral striatum of mice. We then measured protein aggregation in vitro. The rotarod and pole tests were employed next to measure the damage of the phenotype. Pathological deposition and autophagy were also observed by immunofluorescence staining and protein levels measured by western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that short\u2010term hypoxia activated phosphorylated (p)\u2010\u03b1\u2010syn in mice. We confirmed that p\u2010\u03b1\u2010syn was more readily formed aggregates than \u03b1\u2010syn in vitro. Furthermore, we found that hypoxia promoted the activation and propagation of endogenous \u03b1\u2010syn, contributing to the earlier degeneration of dopaminergic neurons in the substantia nigra and the deposition of p\u2010\u03b1\u2010syn in our animal model. Finally, autophagy inhibition contributed to the above pathologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hypoxia was shown to accelerate the pathological progression and damage phenotype in PD model mice. The results provided a promising research target for determining common interventions for PD in the future.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14055","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T05:17:05Z","timestamp":1670995025000},"page":"544-558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hypoxic stress accelerates the propagation of pathological alpha\u2010synuclein and degeneration of dopaminergic neurons"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6178-5225","authenticated-orcid":false,"given":"Mengyuan","family":"Guo","sequence":"first","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data\u2010based Precision Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences Capital Medical University  Beijing China"},{"name":"School of Rehabilitation Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory Affiliated Hospital of Guilin Medical University  Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Shao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data\u2010based Precision Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuning","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data\u2010based Precision Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Gu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data\u2010based Precision Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data\u2010based Precision Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory Affiliated Hospital of Guilin Medical University  Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0527-2852","authenticated-orcid":false,"given":"Xunming","family":"Ji","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data\u2010based Precision Medicine Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-3841","authenticated-orcid":false,"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data\u2010based Precision Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13805"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13045"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x20982389"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa090"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024091"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13234"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228645"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15674"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0197-4580(02)00065-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13916"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.143"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-018-2814-1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.05.035"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.06.018"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3816-2_26"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x221119288"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x17701460"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2021.104801"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2020.152632"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2021.11.004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2018.56"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28544"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13642"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/crj.12718"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.170"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x20943823"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/jpd-171248"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.080390"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10835-8"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms151221875"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3233\/jpd-212847"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc4364"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201809865"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.081950"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1937897"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.919343"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.13"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1515\/reveh-2017-0009"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000005522"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062230"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0457-5"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105392"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13961"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x20943804"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.120.028978"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.101"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.136"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1943-7"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315666"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb748"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.09.004"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11142250"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.09.007"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cns.14055","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T04:24:29Z","timestamp":1692419069000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.14055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1111\/cns.14055"],"URL":"https:\/\/doi.org\/10.1111\/cns.14055","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]},"assertion":[{"value":"2022-10-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}