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This study explores the therapeutic potential of alpha\u2010linolenic acid (ALA), a known antioxidant and anti\u2010inflammatory agent, in a lipopolysaccharide (LPS)\u2010induced murine model of PD. Male Balb\u2010C mice were divided into control, LPS\u2010treated, LPS\u2009+\u2009ALA\u2010treated and ALA\u2010only groups. Behavioural assessments, including the pole test, rotarod test and open field test, revealed significant motor impairments in LPS\u2010treated mice. Co\u2010treatment with ALA partially ameliorated motor deficits in LPS\u2010treated mice compared to the healthy control group. However, no direct comparison was made with standard PD treatments such as levodopa. Immunohistochemistry analysis showed a 68% reduction in tyrosine hydroxylase\u2010positive (TH+) neurons in the substantia nigra pars compacta (SNpc) of LPS\u2010treated mice. Notably, ALA co\u2010treatment preserved dopaminergic neurons, demonstrating its neuroprotective effects. Western blotting and ELISA revealed heightened expression of inflammatory mediators, including TNF\u2010\u03b1, IL\u20101\u03b2 and NF\u2010\u03baB, in LPS\u2010treated mice. ALA treatment significantly reduced these markers, indicating its capacity to mitigate neuroinflammation. Molecular docking analysis revealed moderate binding affinities of ALA to NF\u2010\u03baB (\u22125.1\u2009kcal\/mol), TNF\u2010\u03b1 (\u22125.7\u2009kcal\/mol) and IL\u20101\u03b2 (\u22123.9\u2009kcal\/mol), suggesting possible interactions with key inflammatory pathways. These interactions were comparable to known inhibitors, indicating ALA's potential for neuroprotection. This study highlights the neuroprotective and anti\u2010inflammatory effects of ALA in reducing dopaminergic neuronal loss and mitigating neuroinflammation in an LPS\u2010induced PD model. Although behavioural improvements were moderate, these findings underscore ALA's potential as an adjunct therapeutic candidate for PD and other neurodegenerative diseases. Further research is warranted to explore its translational applications in clinical settings.<\/jats:p>","DOI":"10.1111\/1440-1681.70043","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T07:20:19Z","timestamp":1745479219000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Alpha\u2010Linolenic Acid for Mitigating Neuroinflammation and Dopaminergic Neuronal Loss in Parkinson's Disease: Insights From In\u00a0Vivo and In Silico Studies"],"prefix":"10.1111","volume":"52","author":[{"family":"Mahnoor","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences (IBMS), Khyber Medical University  Peshawar Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3850-1025","authenticated-orcid":false,"given":"Sarwat","family":"Jahan","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences 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