Use of specific inhibitors of stress-activated protein kinases to preserve fast axonal transport function in the treatment of polyglutamine expansion neurodegenerative diseases
The polyglutamine expansion diseases include Kennedy’s Disease (Spinobulbar muscular atrophy), Huntington's disease (HD), and several spinocerebellar ataxias (SCAs). Remarkably, each is caused by CAG codon expansion within a particular gene that produces polyglutamine tract enlargement in the protein. Each such mutant protein causes selective neurodegeneration within the CNS. Formation of nuclear and cytoplasmic aggregates that include such mutant proteins is a characteristic feature of polyglutamine expansion diseases in patients as well as transgenic animal and cell culture models. The precise role of these protein aggregates in pathogenesis remains uncertain.