ArticleMolecular neurobiology2018
Azadiradione Restores Protein Quality Control and Ameliorates the Disease Pathogenesis in a Mouse Model of Huntington's Disease.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 41 citations in OpenAlex.
- Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2025Review
- Prenatal Exposure to Azadiradione Leads to Developmental Disabilities.Molecular neurobiology · 2025Article
- A Comprehensive Review of Therapeutic Compounds from Plants for Neurodegenerative Diseases.Current medicinal chemistry · 2025Review
- Tinospora sinensis (Lour.) Merr alkaloid rich extract induces colon cancer cell death via ROS mediated, mTOR dependent apoptosis pathway: "an in-vitro study".BMC complementary medicine and therapies · 2023Article
- Promising drug targets and associated therapeutic interventions in Parkinson's disease.Neural regeneration research · 2021Review
- Withaferin A Induces Heat Shock Response and Ameliorates Disease Progression in a Mouse Model of Huntington's Disease.Molecular neurobiology · 2021Article
- Exploring cardioprotective potential of esculetin against isoproterenol induced myocardial toxicity in rats: in vivo and in vitro evidence.BMC pharmacology & toxicology · 2021Article
- Terpenoids as Potential Geroprotectors.Antioxidants (Basel, Switzerland) · 2020Review
- Basic Limonoid modulates Chaperone-mediated Proteostasis and dissolve Tau fibrils.Scientific reports · 2020Article
- Quality Control in Huntington's Disease: a Therapeutic Target.Neurotoxicity research · 2019Review
- Neem Derivatives Inhibits Tau Aggregation.Journal of Alzheimer's disease reports · 2019Article
- Targeting the proteostasis network in Huntington's disease.Ageing research reviews · 2019Review
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Authors and funding
8 authors at 3 institutions in 1 country.
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Abstract
Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by expansion of CAG repeats in the coding area of huntingtin gene. In the HD brain, mutant huntingtin protein goes through proteolysis, and its amino-terminal portion consisting of polyglutamine repeats accumulate as inclusions that result in progressive impairment of cellular protein quality control system. Here, we demonstrate that partial rescue of the defective protein quality control in HD model mouse by azadiradione (a bioactive limonoids found in the seed of Azadirachta indica) could potentially improve the disease pathology. Prolonged treatment of azadiradione to HD mice significantly improved the progressive deterioration in body weight, motor functioning along with extension of lifespan. Azadiradione-treated HD mice brain also exhibited considerable decrease in mutant huntingtin aggregates load and improvement of striatal pathology in comparison with age-matched saline-treated HD controls. Biochemical analysis further revealed upregulation and activation of not only HSF1 (master regulator of protein folding) but also Ube3a (an ubiquitin ligase involved in the clearance of mutant huntingtin) in azadiradione-treated mice. Our results indicate that azadiradione-mediated enhanced folding and clearance of mutant huntingtin might underlie improved disease pathology in HD mice and suggests that it could be a potential therapeutic molecule to delay the progression of HD.
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