Therapy development in Huntington disease: From current strategies to emerging opportunities.

ABSTRACT: Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder in which patients typically present with uncontrolled involuntary movements and subsequent cognitive decline. In 1993, a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene was identified as the cause of this disorder. This extended CAG repeat results in production of HTT protein with an expanded polyglutamine tract, leading to pathogenic HTT protein conformers that are resistant to protein turnover, culminating in cellular toxicity and neurodegeneration. Research into the mechanistic basis of HD has highlighted a role for bioenergetics abnormalities stemming from mitochondrial dysfunction, and for synaptic defects, including impaired neurotransmission and excitotoxicity.

SUBMITTER: Dickey AS 

PROVIDER: S-EPMC5975251 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature