Molecular mechanisms of neurodegeneration in Huntington’s Disease

Abstract

Heat shock factor 1 (HSF1) plays a pivotal role in maintaining neuronal health, and its dysfunction contributes significantly to the progression of Huntington’s disease. Rocio Gomez-Pastor tells us more. Huntington’s disease (HD) is a devastating, inherited neurodegenerative disorder marked by progressive motor dysfunction, cognitive decline, and psychiatric symptoms. At its genetic core lies a mutation in the huntingtin (HTT) gene, specifically an expansion of CAG trinucleotide repeats that encode an abnormally long polyglutamine (polyQ) tract in the huntingtin protein. (1) This mutation transforms an otherwise essential cellular protein into a toxic species prone to misfolding and aggregation. Over time, these molecular disturbances selectively damage neurons, particularly in the striatum and cortex. (2,3)