{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:24:12Z","timestamp":1793049852581,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of midbrain substantia nigra dopaminergic neurons, resulting in striatal dopamine depletion and motor dysfunction. While this pathological cascade is well\u2010established, its underlying mechanisms remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To further investigate the pathological mechanisms of PD, we performed single\u2010cell RNA sequencing of the midbrain and striatum from Hua\u2010Syn (SNCA*A53T) transgenic (A53T) mice as a PD model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of 22\u2009865 midbrain and 32\u2009117 striatal cells revealed cell\u2010type\u2010specific risk association. Glial populations (astrocytes, microglia, oligodendrocytes) showed significant enrichment for PD\u2010risk genes. Variance\u2010based clustering identified PD\u2010enriched subclusters exhibiting upregulated inflammatory pathways, apoptotic pathways, proteostasis disruption, glutamatergic signaling dysregulation, and mitochondrial respiratory chain defects. Transcriptional regulation analysis identified genes associated with PD specific activity, including\n                      <jats:italic>Rorb<\/jats:italic>\n                      and\n                      <jats:italic>Foxc1<\/jats:italic>\n                      in the midbrain and\n                      <jats:italic>Dbx2<\/jats:italic>\n                      and\n                      <jats:italic>Klf13<\/jats:italic>\n                      in the striatum. Cell\u2013cell interactions showed that cell\u2010to\u2010cell signaling was enhanced, and the SEMA and CCL neuroinflammatory axes were specifically activated in the PD group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our integrative analysis delineates the cellular and molecular architecture of the pathological process triggered by the expression of A53T mutant \u03b1\u2010synuclein, and provides a framework for targeted therapeutic development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70252","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T17:30:57Z","timestamp":1784050257000},"page":"1613-1632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010cell atlas of neuroglial dynamics in\n                    <scp>SNCA<\/scp>\n                    \u2010\n                    <scp>A53T<\/scp>\n                    Parkinson's disease mouse model"],"prefix":"10.1002","volume":"9","author":[{"given":"Binqing","family":"Qin","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Research Center for Translational Medicine of Xiangyang No. 1 People's Hospital, Hubei Provincial Clinical Research Center for Parkinson's Disease at Xiangyang No. 1 People's Hospital Hubei University of Medicine  Shiyan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichu","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Industrial Engineering, Center for Statistical Science Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanxuan","family":"Zou","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Research Center for Translational Medicine of Xiangyang No. 1 People's Hospital, Hubei Provincial Clinical Research Center for Parkinson's Disease at Xiangyang No. 1 People's Hospital Hubei University of Medicine  Shiyan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senmao","family":"Chai","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Research Center for Translational Medicine of Xiangyang No. 1 People's Hospital, Hubei Provincial Clinical Research Center for Parkinson's Disease at Xiangyang No. 1 People's Hospital Hubei University of Medicine  Shiyan China"},{"name":"Genertec Gem Flower Healthcare Clinical Laboratory of Gem Flower Xian Changqing Staff Hospital  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Weng","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Research Center for Translational Medicine of Xiangyang No. 1 People's Hospital, Hubei Provincial Clinical Research Center for Parkinson's Disease at Xiangyang No. 1 People's Hospital Hubei University of Medicine  Shiyan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Research Center for Translational Medicine of Xiangyang No. 1 People's Hospital, Hubei Provincial Clinical Research Center for Parkinson's Disease at Xiangyang No. 1 People's Hospital Hubei University of Medicine  Shiyan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Sun","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Research Center for Translational Medicine of Xiangyang No. 1 People's Hospital, Hubei Provincial Clinical Research Center for Parkinson's Disease at Xiangyang No. 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