{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:07:09Z","timestamp":1791292029859,"version":"4.1.0"},"reference-count":112,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T00:00:00Z","timestamp":1462320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000040","name":"American Parkinson's Disease Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. 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Ideally, these models should replicate the cardinal features of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>, such as progressive neurodegeneration of catecholaminergic neurons and motor defects. Many current <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> models emphasize pathological forms of \u03b1\u2010synuclein, based on findings that autosomal dominant mutations in \u03b1\u2010synuclein and duplications\/triplications of the <jats:styled-content style=\"fixed-case\">SNCA<\/jats:styled-content> gene cause <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. In addition, Lewy bodies and Lewy neurites, primarily composed of \u03b1\u2010synuclein, represent the predominant pathological characteristics of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. These inclusions have defined features, such as insolubility in non\u2010ionic detergent, hyperphosphorylation, proteinase K sensitivity, a filamentous appearance by electron microscopy, and \u03b2\u2010sheet structure. Furthermore, it has become clear that Lewy bodies and Lewy neurites are found throughout the peripheral and central nervous system, and could account not only for motor symptoms, but also for non\u2010motor symptoms of the disease. The goal of this review is to describe two new \u03b1\u2010synuclein\u2010based models: the recombinant adeno\u2010associated viral vector\u2010\u03b1\u2010synuclein model and the \u03b1\u2010synuclein fibril model. An advantage of both models is that they do not require extensive crossbreeding of rodents transgenic for \u03b1\u2010synuclein with other rodents transgenic for genes of interest to study the impact of such genes on <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010related pathology and phenotypes. In addition, abnormal \u03b1\u2010synuclein can be expressed in brain regions relevant for disease. Here, we discuss the features of each model, how each model has contributed thus far to our understanding of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>, and the advantages and potential caveats of each model.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<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\/jnc13627-fig-0003-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nThis review describes two \u03b1\u2010synuclein\u2010based rodent models of Parkinson's disease: the rAAV\u2010\u03b1\u2010synuclein model and the \u03b1\u2010synuclein fibril model. The key features of these models are described, and the extent to which they recapitulate features of PD, such as \u03b1\u2010synuclein inclusion formation, loss of dopaminergic synapses in the striatum, motor defects, inflammation, and dopamine neuron death.<\/jats:p><jats:p><jats:bold>This article is part of a <\/jats:bold><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/journal\/10.1111\/(ISSN)1471-4159\/homepage\/special_issues.htm\">special issue on Parkinson disease<\/jats:ext-link><jats:bold>.<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13627","type":"journal-article","created":{"date-parts":[[2016,3,28]],"date-time":"2016-03-28T13:02:15Z","timestamp":1459170135000},"page":"131-155","source":"Crossref","is-referenced-by-count":113,"title":["How can <scp>rAAV<\/scp>\u2010\u03b1\u2010synuclein and the fibril \u03b1\u2010synuclein models advance our understanding of Parkinson's disease?"],"prefix":"10.1111","volume":"139","author":[{"given":"Laura A.","family":"Volpicelli\u2010Daley","sequence":"first","affiliation":[{"name":"From the Center for Neurodegeneration and Experimental Therapeutics Department of Neurology The University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Kirik","sequence":"additional","affiliation":[{"name":"Brain Repair and Imaging in Neural Systems Department of Experimental Medical Science Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay E.","family":"Stoyka","sequence":"additional","affiliation":[{"name":"From the Center for Neurodegeneration and Experimental Therapeutics Department of Neurology The University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Standaert","sequence":"additional","affiliation":[{"name":"From the Center for Neurodegeneration and Experimental Therapeutics Department of Neurology The University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley S.","family":"Harms","sequence":"additional","affiliation":[{"name":"From the Center for Neurodegeneration and Experimental Therapeutics Department of Neurology The University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0614-15.2015"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-140491"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.226"},{"key":"e_1_2_12_5_1","first-page":"872","article-title":"Phosphorylation does not prompt, nor prevent, the formation of alpha\u2010synuclein toxic species in a rat model of Parkinson's disease","volume":"18","author":"Azeredo da Silveira S.","year":"2009","journal-title":"Hum. 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