{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:32:58Z","timestamp":1788849178568,"version":"build-2803163510"},"reference-count":43,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JHD"],"published-print":{"date-parts":[[2024,3,29]]},"abstract":"<jats:p>Background: Huntington\u2019s disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction caused by a mutant huntingtin protein. Compromised metabolic activity resulting from systemic administration of the mitochondrial toxin, 3-nitropropionic acid (3-NP), is known to mimic the pathology of HD and induce HD-like symptoms in rats. N-hexanoic-Tyr-Ile-(6)-amino hexanoic amide (PNB-0408), also known as Dihexa, has been shown to have neuroprotective and procognitive properties in animal models of Alzheimer\u2019s and Parkinson\u2019s diseases. Given the mechanism of action and success in other neurodegenerative diseases, we felt it an appropriate compound to investigate further for HD. Objective: The present study was designed to test if PNB-0408, an angiotensin IV analog, could attenuate 3-NP-induced HD-like symptoms in rats and serve as a potential therapeutic agent. Methods: Forty male Wistar rats were randomized into three groups consisting of a \u201cvehicle\u201d group, a \u201c3-NP\u201d group, and a \u201c3-NP\u200a+\u200aPNB-0408\u201d group. PNB-0408 was administered along with chronic exposure to 3-NP. Animal body weight, motor function, and cognitive abilities were measured for five weeks, before euthanasia and histopathological analysis. Results: Exposure to 3-NP decreased the amount of weight rats gained, impaired spatial learning and memory consolidation, and led to marked motor dysfunction. From our observations and analysis, PNB-0408 did not protect rats from the deficits induced by 3-NP neurotoxicity. Conclusions: Our findings suggest that PNB-0408 may not be an efficacious treatment strategy for preventing 3-NP-induced HD-like symptoms in a preclinical model. These data highlight the need for further research of this compound in alternate models and\/or alternative approaches to managing this disorder.<\/jats:p>","DOI":"10.3233\/jhd-231507","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T12:59:58Z","timestamp":1710248398000},"page":"55-66","source":"Crossref","is-referenced-by-count":2,"title":["Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington\u2019s Disease-Like Symptoms in Rats"],"prefix":"10.1177","volume":"13","author":[{"given":"Russell G.","family":"Wells","sequence":"first","affiliation":[{"name":"Department of Biology, Whitworth University, Spokane, WA, USA"},{"name":"School of Medicine, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azzam F.","family":"Azzam","sequence":"additional","affiliation":[{"name":"Department of Biology, Whitworth University, Spokane, WA, USA"},{"name":"School of 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