Fragile X-associated tremor/ataxia syndrome (FXTAS): Pathology and mechanisms

摘要: Since its discovery in 2001, our understanding of fragile X-associated tremor/ataxia syndrome (FXTAS) has undergone a remarkable transformation. Initially characterized rather narrowly as an adult-onset movement disorder, the definition FXTAS is broadening; moreover, disorder now recognized only one facet much broader clinical pleiotropy among children and adults who carry premutation alleles FMR1 gene. Furthermore, intranuclear inclusions FXTAS, once thought to be CNS-specific marker are known widely distributed multiple non-CNS tissues; this observation fundamentally changes concept disease, may provide basis for diverse medical problems associated with premutation. Recent work on pathogenic mechanisms underlying indicates that origins late-onset neurodegenerative actually lie early development, raising likelihood all forms involvement carriers have common mechanistic basis. There also been great progress triggering event(s) pathogenesis, which involve sequestration or more nuclear proteins involved microRNA biogenesis. Moreover, there mounting evidence mitochondrial dysregulation contributes decreased cell function loss viability, evident mice even during neonatal period. Taken together, these recent findings offer hope interventions well before onset overt treatment other carriers.