Excitatory synapse impairment and mitochondrial dysfunction in Huntington’s disease: heat shock factor 1 (HSF1) converging mechanisms
Nicole Zarate
Rocio Gomez-Pastor
摘要：Heat shock factor 1 (HSF1) is abnormally degraded in Huntington’s disease (HD): HD is a neurodegenerative disorder characterized by se-vere cognitive and motor impairments. HD is caused by a CAG repeat expansion within exon 1 of the huntingtin (HTT) gene (The Hunting-ton’s Disease Collaborative Research Group, 1993). These expansions lead to the production of an aberrant mutant huntingtin protein (mHTT) that is prone to misfolding and aggregation. Expression and aggregation of mHTT is present in virtually all cell types in the body but preferentially affects medium spiny neurons of the striatum, a brain region that controls movement and some forms of cognition. Accumu-lation of mHTT leads to, but not only, transcriptional dysregulation, DNA damage, mitochondrial dysfunction and excitatory synaptic fail-ure ultimately causing neuronal death. However, the molecular mecha-nisms by which mHTT exerts these defects are still unclear.
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论文发表日期：2020-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：2( 69-70 )