From Pathogenesis to Novel Therapeutics for Spinocerebellar Ataxia Type 3: Evading Potholes on the Way to Translation

摘要: Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a neurodegenerative disorder caused by polyglutamine expansion in the ATXN3 gene. In spite of identification clear monogenic cause 25 years ago, pathological process still puzzles researchers, impairing prospects for an effective therapy. Here, we propose disruption protein homeostasis hub SCA3 pathogenesis, being molecular mechanisms and cellular pathways that are deregulated downstream consequences misfolding aggregation ATXN3. Moreover, attempt to provide realistic perspective on how translational/clinical research should evolve. This was based findings, clinical epidemiological characteristics, studies proposed treatments other conditions, information essential their (re-)application SCA3. review thus aims i) critically evaluate current state SCA3, from fundamental translational perspectives; ii) bring up key questions remain unanswered this disorder; iii) frame those answers be pursued.