Heat shock factor 1(HSF1)is abnormally degraded in Huntington’s disease(HD):HD is a neurodegenerative disorder characterized by severe cognitive and motor impairments.HD is caused by a CAG repeat expansion within exo...Heat shock factor 1(HSF1)is abnormally degraded in Huntington’s disease(HD):HD is a neurodegenerative disorder characterized by severe cognitive and motor impairments.HD is caused by a CAG repeat expansion within exon 1 of the huntingtin(HTT)gene(The Huntington’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.Accumulation of mHTT leads to,but not only,transcriptional dysregulation,DNA damage,mitochondrial dysfunction and excitatory synaptic failure ultimately causing neuronal death.However,the molecular mechanisms by which mHTT exerts these defects are still unclear.展开更多
文摘Heat shock factor 1(HSF1)is abnormally degraded in Huntington’s disease(HD):HD is a neurodegenerative disorder characterized by severe cognitive and motor impairments.HD is caused by a CAG repeat expansion within exon 1 of the huntingtin(HTT)gene(The Huntington’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.Accumulation of mHTT leads to,but not only,transcriptional dysregulation,DNA damage,mitochondrial dysfunction and excitatory synaptic failure ultimately causing neuronal death.However,the molecular mechanisms by which mHTT exerts these defects are still unclear.
