{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:43:54Z","timestamp":1772160234215,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["19\/FFP\/6554"],"award-info":[{"award-number":["19\/FFP\/6554"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Numerous challenges hinder the development of neuroprotective treatments for Parkinson's disease, with a regularly identified issue being the lack of clinically relevant animal models. Viral vector overexpression of \u03b1\u2010synuclein is widely considered the most relevant model; however, this has been limited by high variability and inconsistency. One potential method of optimisation is pairing it with a secondary insult such as FN075, a synthetic molecule demonstrated to accelerate \u03b1\u2010synucleinopathy. Thus, the aim of this study was to investigate if sequential infusion of adeno\u2010associated virus (AAV)\u2010\u03b1\u2010synuclein and FN075 into the rat brain can replicate \u03b1\u2010synucleinopathy, nigrostriatal pathology and motor dysfunction associated with Parkinson's disease. Rats received a unilateral injection of AAV\u2010\u03b1\u2010synuclein (or AAV\u2010green fluorescent protein) into two sites in the substantia nigra, followed 4\u00a0weeks later by unilateral injection of FN075 (or vehicle) into the striatum. Animals underwent behavioural testing every 4\u00a0weeks until sacrifice at 20\u2009weeks, followed by immunohistochemistry assessment post\u2010mortem. As anticipated, AAV\u2010\u03b1\u2010synuclein led to extensive overexpression of human \u03b1\u2010synuclein throughout the nigrostriatal pathway, as well as elevated levels of phosphorylated and aggregated forms of the protein. However, the sequential administration of FN075 into the striatum did not exacerbate any of the \u03b1\u2010synuclein pathology. Furthermore, despite the extensive \u03b1\u2010synuclein pathology, neither administration of AAV\u2010\u03b1\u2010synuclein nor FN075, alone or in combination, was sufficient to induce dopaminergic degeneration or motor deficits. In conclusion, this approach did not replicate the key characteristics of Parkinson's disease, and further studies are required to create more representational models for testing of novel compounds and treatments for Parkinson's disease.<\/jats:p>","DOI":"10.1111\/ejn.16493","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T01:19:02Z","timestamp":1723684742000},"page":"5234-5248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intra\u2010striatal infusion of the small molecule alpha\u2010synuclein aggregator, FN075, does not enhance parkinsonism in a subclinical AAV\u2010alpha\u2010synuclein rat model"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-2705","authenticated-orcid":false,"given":"Tommy","family":"Patton","sequence":"first","affiliation":[{"name":"Pharmacology &amp; Therapeutics and Galway Neuroscience Centre University of 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