{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:44:42Z","timestamp":1786977882241,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Alpha\u2010synuclein pathology is a characteristic feature of Parkinson's disease (PD) and related synucleinopathies. As a result, reducing alpha\u2010synuclein pathology is one of the mechanisms being looked at for the development of newer agents which target these diseases. In the present study, we investigated the potential of HC070, a transient receptor potential canonical 5 (TRPC5) channel inhibitor in reducing alpha\u2010synuclein pathology in PD. TRPC5 channels are activated in response to oxidative stress and mediators of apoptosis (calpain), the processes are also closely linked to alpha\u2010synuclein toxicity. Using exposure of alpha synuclein\u2010preformed fibrils to the Sprague Dawley rats and SH\u2010SY5Y cells, we induced PD in in vitro and in vivo model systems. It was followed by the estimation of behavioural deficits, molecular parameters and biochemical estimations. Results of our experiments revealed that animals treated intraperitoneally with HC070 exhibited reduced alpha\u2010synuclein levels accompanied by improvement in tyrosine hydroxylase levels, mitochondrial health and reduction in oxidative stress and calpain signalling. Furthermore, HC070 administration also caused a reduction in the TRPC5 levels along with improvement seen in motor and cognitive deficits. Similar protection was observed with HC070 in SH\u2010SY5Y cells exposed to alpha\u2010synuclein PFF. Overall, our study demonstrates the novel role of inhibition of TRPC5 channels in the reversal of alpha\u2010synuclein toxicity and associated PD pathology.<\/jats:p>","DOI":"10.1002\/jbt.70207","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T06:06:49Z","timestamp":1741673209000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["HC070, a Transient Receptor Potential Canonical 5 (TRPC5) Channels Inhibitor Ameliorated \u03b1\u2010synuclein Preformed Fibrils\u2010Induced Parkinson's Disease: A Neurobehavioural and Mechanistic Study"],"prefix":"10.1002","volume":"39","author":[{"given":"Bhupesh","family":"Vaidya","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and Research, S.A.S. 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