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Treatment of ND is challenging, as the symptoms in these patients arises when a significant numbers of neurons have already been destroyed. Heat shock proteins (HSPs) can bind to recipient cells that are susceptible to stress, such as neurons, in the extracellular environment, therefore enhancing stress resistance. Among all, HSP60, HSP70, and HSP90 are highly conserved molecular chaperones involved in protein folding and assembly, maintaining cellular homeostasis in the central nervous system. Notably, \u03b1\u2010synuclein accumulation is a major pathophysiology in Parkinson's disease, where HSP90 modulates the assembly of \u03b1\u2010synuclein in vesicles to prevent its accumulation. Moreover, HSP90 regulates the activity of the glycogen synthase kinase\u20103\u03b2 protein, which is crucial in diabetes mellitus\u2010associated neurocognitive disorder. Therefore, understanding the molecular mechanism by which HSPs facilitate protein aggregation and respond to inflammatory stimuli, including metabolic disease such as diabetes, is essential for understanding the significance of HSPs in NDs. This review emphasizes the role of various HSPs in the progression of NDs such as Alzheimer's, Parkinson's, multiple sclerosis, and Huntington's disease, including diabetes, which is one of the major risk factors for neurodegeneration.<\/jats:p>","DOI":"10.1002\/nep3.68","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T03:29:17Z","timestamp":1736306957000},"page":"48-62","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Decoding the role of large heat shock proteins in the progression of neuroinflammation\u2010mediated neurodegenerative disorders"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2856-4185","authenticated-orcid":false,"given":"Shailendra K.","family":"Saxena","sequence":"first","affiliation":[{"name":"Centre for Advanced Research (CFAR), Faculty of Medicine King George's Medical University (KGMU) Lucknow 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