Neuronal Death in Huntington's Disease: Multiple Pathways for One Issue?

摘要

Huntington's disease (HD) is a mid-life onset neurodegenerative disorder characterized by involuntary movements (chorea), personality changes and dementia. The neuropathology of HD is a marked neuronal death in the striatum while other brain structures are selectively spared. The defective gene in HD contains a trinucleotide CAG repeat expansion within its coding region that is expressed as a polyglutamine repeat in the protein huntingtin. CAG expansions represent a novel type of mutation in the human genome and have also been found in several other inherited neurodegenerative disorders. The mechanisms by which mutant huntingtin induces neuronal death are not well understood. However, studies suggest a cascade of events that begins in the cytoplasm and ends with the translocation and accumulation of the mutant protein in the nucleus. During this course, mutant huntingtin might affect a wide range of intracellular systems such as vesicular transport and trafficking and the apoptotic machinery as well as transcription. Modification of one if not all of those intracellular systems could ultimately lead to the death of the striatal neurons in HD.