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Abstract

Huntington's disease (HD) is a severe neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, leading to the production of a mutant huntingtin protein. This mutation results in progressive motor, cognitive, and psychiatric impairments, alongside significant neuronal loss. Mitochondrial dysfunction plays a pivotal role in the pathophysiology of HD, contributing to disease progression and neuronal death. This article aims to evaluate small molecule-based therapeutic strategies designed to enhance mitochondrial function as a potential approach to alleviate symptoms and slow the progression of HD and related neurodegenerative disorders. A comprehensive review of recent literature is conducted to identify small molecules targeting mitochondrial dysfunction from Google Scholar, PubMed/Medline/PMC, ScienceDirect, Elsevier, Google Patents, and Clinicaltrials.gov.in, among others. The analysis focuses on their mechanisms of action, including reducing oxidative stress, enhancing mitochondrial biogenesis, and improving mitochondrial dynamics and function. The review identifies several promising small molecules capable of targeting mitochondrial dysfunction. These agents demonstrate potential in preclinical studies to alleviate HD symptoms and modify disease progression by addressing key aspects of mitochondrial health. Small molecule therapies targeting mitochondrial dysfunction offer considerable promise for treating HD. However, further research is required to optimize these therapies for clinical use and to evaluate their long-term impact on disease progression to fully establish their therapeutic efficacy.

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2025-09-11
2025-12-17

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Advancing Mitochondrial Health in Huntington Disease (HD): Small Molecule Therapies and Neurodegeneration
Bentham Science Publishers ; https://doi.org/10.2174/0118746098387655250818072130
/content/journals/cas/10.2174/0118746098387655250818072130
/content/journals/cas/10.2174/0118746098387655250818072130
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  • Article Type:     Review Article
Keywords: neurodegeneration ; gene therapy ; mutant huntingtin ; targeted drug delivery ; Huntington’s disease ; mitochondrial dysfunction ; nanomedicine ; pharmacological applications

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