ArticleMolecular neurobiology2021
Withaferin A Induces Heat Shock Response and Ameliorates Disease Progression in a Mouse Model of Huntington's Disease.
Article in Molecular neurobiology, 2021. 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, 32 citations in OpenAlex.
- Transcriptional responses to proteotoxic stressors are profoundly diverse and tissue-specific.Cell stress & chaperones · 2026Article
- Natural products proposed for the management of Huntington's disease (HD): a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons.Stem cells (Dayton, Ohio) · 2025Article
- A Comprehensive Review of Therapeutic Compounds from Plants for Neurodegenerative Diseases.Current medicinal chemistry · 2025Review
- Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer.Current issues in molecular biology · 2024Review
- Review
- Pathways to healing: Plants with therapeutic potential for neurodegenerative diseases.IBRO neuroscience reports · 2023Article
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- AshwagandhaPharmaceutics · 2023Review
- Closest horizons of Hsp70 engagement to manage neurodegeneration.Frontiers in molecular neuroscience · 2023Review
- HSF1 Alleviates Brain Injury by Inhibiting NLRP3-Induced Pyroptosis in a Sepsis Model.Mediators of inflammation · 2023Article
- A Novel Huntington's Disease Assessment Platform to Support Future Drug Discovery and Development.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impairment of proteostasis network is one of the characteristic features of many age-related neurodegenerative disorders including autosomal dominantly inherited Huntington's disease (HD). In HD, N-terminal portion of mutant huntingtin protein containing expanded polyglutamine repeats accumulates as inclusion bodies and leads to progressive deterioration of various cellular functioning including proteostasis network. Here we report that Withaferin A (a small bioactive molecule derived from Indian medicinal plant, Withania somnifera) partially rescues defective proteostasis by activating heat shock response (HSR) and delays the disease progression in a HD mouse model. Exposure of Withaferin A activates HSF1 and induces the expression of HSP70 chaperones in an in vitro cell culture system and also suppresses mutant huntingtin aggregation in a cellular model of HD. Withaferin A treatment to HD mice considerably increased their lifespan as well as restored progressive motor behavioral deficits and declined body weight. Biochemical studies confirmed the activation of HSR and global decrease in mutant huntingtin aggregates load accompanied with improvement of striatal function in Withaferin A-treated HD mouse brain. Withaferin A-treated HD mice also exhibit significant decrease in inflammatory processes as evident from the decreased microglial activation. These results indicate immense potential of Withaferin A for the treatment of HD and related neurodegenerative disorders involving protein misfolding and aggregation.
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