Putting the Brakes on Huntington Disease in a Mouse Experimental Model

TL;DRAbstract

Huntington disease (HD) is a hereditary neurodegenerative disorder that causes a progressively debilitating impact on movement, cognition, speech, and mood. It most commonly develops during adulthood and worsens over a 10–15-year period. The genetic basis of HD is an expansion of the (CAG)n trinucleotide repeat in the first exon of the HTT gene [1,2]. Although the function of the normal HTT protein is not well established, in-frame repeat expansion results in the accumulation of an abnormally long polyglutamine tract, which is believed to contribute to mutant protein toxicity and neural degeneration [3]. Consequently, CAG repeat length is inversely correlated with age of onset and severity of disease. Disease-size CAG repeats are prone to further lengthening, which leads to two distinct aspects of their instability: expansions during intergenerational transmissions and somatic expansions occurring throughout the lifetime of an individual (Fig 1A).

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