Machado-Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy.

摘要: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an incurable disorder, widely regarded the most common form of in world. MJD/SCA3 arises from mutation ATXN3 gene, but this simple monogenic cause contrasts with complexity pathogenic mechanisms that are currently admitted to underlie neuronal dysfunction and death. The aberrantly expanded protein product - ataxin-3 aggregate generate toxic species disrupt several cell systems, including autophagy, proteostasis, transcription, mitochondrial function signalling. Over years, research into putative therapeutic approaches has often been devoted development strategies counteract at different stages cellular pathogenesis. Silencing protein, blocking aggregation, inhibiting proteolytic processing counteracting dysfunctions systems affected have yielded promising ameliorating results studies animal models. current review analyses available dedicated investigation pathogenesis exploration possible strategies, focusing primarily on gene therapy pharmacological rooted molecular disease.