neuro-congress-2019-scientifictracks

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Neuro Congress 2019

Journal of Brain and Neurology | Volume 3

June 19-20, 2019 | Dublin, Ireland

OF EXCELLENCE

IN INTERNATIONAL

MEETINGS

YEARS

NEUROLOGY AND BRAIN DISORDERS

International Conference on

MYRICETIN REDUCES TOXIC LEVEL OF CAG REPEATS RNA IN HUNTINGTON’S DISEASE

(HD) AND SPINOCEREBELLAR ATAXIA (SCAS)

Eshan Khan, Subodh Kumar Mishra

and

Amit Kumar

Indian Institute of Technology, India

untington’s disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG

repeats in the HTT gene. The transcribed mutant RNA contains expanded CAG repeats that translate into

a mutant huntingtin protein. This expanded CAG repeat also causes mis-splicing of pre-mRNA due to seques-

tration of muscle blind like-1 splicing factor (MBNL1) and thus both of these elicit the pathogenesis of HD.

Targeting the onset as well as progression of HD by small molecules could be a potent therapeutic approach.

Author has screened a set of small molecules to target this transcript and found Myricetin, a flavonoid as a lead

molecule that interacts with the CAG motif and thus prevents the translation of mutant huntingtin protein as

well as sequestration of MBNL1. Here, they report the first solution structure of the complex formed between

Myricetin and RNA containing the 5’CAG/3’GAC motif. Myricetin interacts with this RNA via base stacking at

the AA mismatch. Moreover, Myricetin was also found reducing the proteo-toxicity generated due to the ag-

gregation of polyglutamine and further, its supplementation also improves neurobehavioral deficits in the HD

mouse model. Their study provides the structural and mechanistic basis of Myricetin as an effective therapeutic

candidate for HD and other polyQ related disorders.

Eshan Khan et al., J Brain Neurol 2019, Volume 3

Eshan Khan is a PhD Research Scholar under supervision of Dr Amit Kumar in Discipline of Biosciences and Biomedical Engineering,

Indian Institute of Technology Indore, India. He has joined Amit Kumar’s lab in July, 2014 and working on therapeutic approaches

targeting (CAG) exp RNA that causes neurological disorders like Huntington’s disease (HD) and Spino cerebellar ataxia (SCAs).

BIOGRAPHY