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Curcumin modulates cell death and is protective in Huntington's disease model
Anjalika Chongtham1, Namita Agrawal1
1Department of Zoology, University of Delhi, Delhi, India-110007.
Insights
Curcumin, a natural compound, shows promise in treating Huntington's disease (HD). This study found curcumin significantly reduces cell death and ameliorates symptoms in a Drosophila model of HD, offering a potential treatment with minimal side effects.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Huntington's disease (HD) is a progressive neurodegenerative disorder caused by expanded polyglutamine (polyQ) repeats in the Huntingtin (Htt) protein.
- Current treatments for HD lack disease-modifying effects and often have significant side effects.
- Pathological hallmarks of HD include inclusion bodies, cellular toxicity, motor deficits, and reduced viability, driven by oxidative stress, mitochondrial dysfunction, and inflammation.
Purpose of the Study:
- To investigate the therapeutic potential of curcumin, a phytochemical with known antioxidant and anti-inflammatory properties, in a Drosophila model of Huntington's disease.
Main Methods:
- Utilized a Drosophila melanogaster model expressing mutant Huntingtin (Htt) protein with expanded polyQ repeats.
- Administered curcumin to assess its impact on HD-related pathology, including cell death, motor function, and viability.
- Evaluated curcumin's effects on cellular toxicity and inclusion body formation.
Main Results:
- Curcumin administration significantly ameliorated disease symptoms in the Drosophila model of HD.
- Curcumin suppressed cell death, a key pathological event in Huntington's disease progression.
- The phytochemical demonstrated potential in halting disease progression with minimal observed side effects.
Conclusions:
- Curcumin exhibits significant therapeutic potential for Huntington's disease.
- Suppression of cell death by curcumin offers a promising avenue for halting HD progression.
- Curcumin represents a potential disease-modifying treatment for Huntington's disease with a favorable side effect profile.
Abstract:
Huntington's disease (HD) is a progressive, dominantly inherited neurological disorder caused by an abnormal expansion of polyglutamine (polyQ) repeat within the Huntingtin (Htt) protein with no disease modifying treatments. In a Drosophila model of HD, expression of mutant Huntingtin (Htt) protein with expanded polyQ leads to formation of inclusion bodies (IBs), increase in cellular toxicity, progression of motor disabilities and reduced viability. Multiple cellular events such as oxidative stress, mitochondrial dysfunction, inflammation and transcriptional dysregulation are reported to contribute to pathology, however, till date there are no disease-modifying treatments with least side effects. Therefore, we investigated effect of the phytochemical curcumin on HD pathogenesis. Curcumin, a phytochemical and commonly used ingredient in Asian food has a wide spectrum of anti-oxidant, anti-inflammatory and anti-fibrilogenic properties. In this study, we provide evidence that curcumin significantly ameliorates disease symptoms in a Drosophila model of HD by suppressing cell death and can be a key to halting the progression of Huntington's disease with least side effects.
