Development and neurodegeneration
Turning HD pathogenesis on its head
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The term “neurodegenerative” implies a period of normal development preceding cell death. Determining when decline begins and the selective vulnerability of specific brain regions to the degenerative cascade is key to development of disease-modifying therapies. Huntington disease (HD), an autosomal dominant disease with little contribution from modifier genes, and complete penetrance in individuals with CAG repeat length ≥40 in the Huntington (Htt) gene, permits the identification of an at-risk population for whom the probability of age at diagnosis can be modeled based on CAG repeat length and age. What if Huntington disease is both a neurodevelopmental disorder and a neurodegenerative disease?
The possibility that mutant Htt (mHtt) might result in fundamental embryonic developmental abnormalities that correlate with the patterns of …
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