{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:28:18Z","timestamp":1781303298613,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003452","name":"Innovation and Technology Commission","doi-asserted-by":"publisher","award":["ITCPD\/17\u20109"],"award-info":[{"award-number":["ITCPD\/17\u20109"]}],"id":[{"id":"10.13039\/501100003452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parkinson's disease (PD) is a common neurodegenerative disorder that is affecting an increasing number of older adults. Although PD is mostly sporadic, genetic mutations have been found in cohorts of families with a history of familial PD (FPD). The first such mutation linked to FPD causes a point mutation (A53T) in \u03b1\u2010synuclein (\u03b1\u2010syn), a major component of Lewy bodies, which are a classical pathological hallmark of PD. These findings suggest that \u03b1\u2010syn is an important contributor to the development of PD. In our previous study, we developed an adenoviral mouse model of PD and showed that the expression of wild\u2010type (WT) \u03b1\u2010syn or a mutant form with an increased propensity to aggregate, designated as WT\u2010CL1 \u03b1\u2010syn, could be used to study how \u03b1\u2010syn aggregation contributes to PD. In this study, we established a transgenic mouse model that conditionally expresses WT or WT\u2010CL1 \u03b1\u2010syn in dopaminergic (DA) neurons and found that the expression of either WT or WT\u2010CL1 \u03b1\u2010syn was associated with an age\u2010dependent degeneration of DA neurons and movement dysfunction. Using this model, we were able to monitor the process of \u03b1\u2010syn aggregate formation and found a correlation between age and the number and sizes of \u03b1\u2010syn aggregates formed. These results provide a potential mechanism by which age\u2010dependent \u03b1\u2010syn aggregation may lead to the formation of Lewy bodies in PD pathogenesis.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16122-fig-0011-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.16122","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T02:33:50Z","timestamp":1714617230000},"page":"1215-1236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The role of age\u2010associated alpha\u2010synuclein aggregation in a conditional transgenic mouse model of Parkinson's disease: Implications for Lewy body formation"],"prefix":"10.1111","volume":"168","author":[{"given":"Jiahua","family":"Li","sequence":"first","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Wai","family":"Ng","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Chau","family":"Sung","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4002-1338","authenticated-orcid":false,"given":"Kenny K. K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(00)80886\u20107"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.5607\/en21013"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6194\u201010.2011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8060565"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20228"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.329.7466.611"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pbr.2020.02.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010018\u20100236\u20108"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896\u20106273(95)90040\u20103"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(02)00682\u20107"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010007\u20100302\u2010x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298\u2010106"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.132197599"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23894"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1913904117"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5456.1265"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2010.05.010"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.28.061604.135718"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv297"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15777"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.22.1.123"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202012095"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828727ba"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509567103"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090278"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.09.016"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.23.11282"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038545"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44154"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052868"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2012.07769.x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10795"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2011.02.011"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.16122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T13:14:51Z","timestamp":1718975691000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.16122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":36,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/jnc.16122"],"URL":"https:\/\/doi.org\/10.1111\/jnc.16122","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-11-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}