Curcumin enhances the polyglutamine-expanded truncated N-terminal huntingtin-induced cell death by promoting proteasomal malfunction

Biochemical and Biophysical Research Communications
Priyanka DikshitNihar Ranjan Jana

Abstract

Formation of neuronal intranuclear inclusions of the disease proteins that are ubiquitinated and often associated with various proteasome components is the major hallmark of the polyglutamine diseases. Curcumin is a polyphenolic compound having anti-inflammatory, anti-tumor, and anti-oxidative properties. Recently, curcumin has been reported to suppress the amyloid-beta accumulation, oxidative damage, and inflammation in the transgenic mice model of Alzheimer's disease. Here, we found that the treatment of curcumin increases the polyglutamine-expanded truncated N-terminal huntingtin (mutant huntingtin) aggregation and mutant huntingtin-dependent cell death. Curcumin also causes rapid proteasomal malfunction in the mutant huntingtin expressing cells in comparison with normal glutamine repeat expressing cells. Finally, we show that N-acetyl cysteine (NAC), a potent antioxidant, reverted the curcumin-induced mutant huntingtin aggregation and proteasomal malfunction in the mutant huntingtin expressing cells. NAC also protects curcumin-induced cell death. Our result suggests that curcumin promotes mutant huntingtin-induced cell death by mimicking proteasomal dysfunction.

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Citations

May 25, 2013·Journal of Clinical Biochemistry and Nutrition·Akira Murakami
Aug 18, 2012·Journal of Biophysics·María Elena Chánez-Cárdenas, Edgar Vázquez-Contreras
May 12, 2009·Brain Research Bulletin·Irène M RiedererBeat M Riederer
Apr 4, 2008·Molecular Nutrition & Food Research·Ajay GoelBharat B Aggarwal
Dec 7, 2006·The Journal of Biological Chemistry·Sivaprakasam Balasubramanian, Richard L Eckert
Apr 3, 2014·Chemistry : a European Journal·Sharbari PalmalNikhil R Jana
Jul 17, 2013·Experimental Biology and Medicine·Beat M RiedererZeinab Elhajj
Jun 3, 2018·International Journal of Molecular Sciences·Panchanan Maiti, Gary Leo Dunbar

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