Trinucleotide repeat disease

摘要: It has been more than 10 years since the discovery that expansion of a simple CAG trinucleotide repeat within coding region androgen receptor gene leads to motor neuronopathy spinal and bulbar muscular atrophy (SBMA). A flurry investigation into this other, recently discovered, polyglutamine diseases led an understanding many aspects molecular pathogenesis family diseases. characteristics pathological feature is occurrence in affected neurons ubiquitinated aggregates; such aggregates also contain, among others, proteins involved folding degradation mutant proteins. Aggregates themselves are likely not directly cytotoxic, but rather mark accumulation all or part protein. Furthermore, aggregation occurs because inefficient clearance protein by ubiquitin-proteasome pathway for degradation. These findings common reflect general problem folding/degrading expanded polyglutamines. In SBMA, altered metabolism ligand dependent. How causes neuronal dysfunction disease well understood, several cellular processes have implicated. Although these provide insight toxic function protein, additional investigations finding intrinsic AR transactivational somewhat diminished presence polyglutamine; partial insensitivity characterizes patients with SBMA. The recent development useful animal cell models SBMA will lead increased pathogenesis, as new better therapeutic strategies.