Chapter 33 – Modeling Huntington Disease in Yeast and Invertebrates

摘要: Huntington disease (HD) is a fatal, late-onset neurodegenerative disorder caused by the expansion of CAG trinucleotide repeat in huntingtin gene (HTT), which encodes polyglutamine (polyQ) tract with high propensity to misfold and aggregate. Mutant HTT believed act predominantly via gain-of-toxic-function mechanism, leading myriad downstream dysfunctions at cellular level, culminating generation symptoms. The gain-of-function nature this mutation has permitted development several transgenic models HD that express all or portion human containing polyQ stretch, including yeast, nematode, fruit fly, mouse. While murine have become mammalian system choice—and gold standard for preclinical testing drug-like compounds—yeast invertebrate been used extensively made major contributions both understanding pathogenesis identification candidate therapeutic targets compounds disorder. Here we provide an overview these discuss how they contributed our HD.