Research progress on the mechanism of mitochondrial dysfunction in spinocerebellar ataxia type 3
Liu Yixuan
Pu Juanjuan
Tang Mibo
Abstract：Spinocerebellar ataxia type 3(SCA3)is an autosomal dominant neurodegenerative disease and one of the most common neurogenetic degenerative disorders.The core pathogenic factor is the abnormal expansion of CAG trinucleotide repeat sequences in the ATXN3 gene,which leads to the accumulation of mutant ataxin-3 protein.Its pathogenesis has not been fully elucidated,and there is no effective therapeutic drug available.Mitochondrial dysfunction is a key pathological mechanism of SCA3.This article focuses on the role of mitochondrial dysfunction in SCA3.Mitochondrial dysfunction in SC A3 is characterized by bioenergetic defects such as decreased membrane potential,elevated reactive oxygen species and reduced adenosine triphosphate production.The underlying mechanisms involve the interference of mutant ataxin-3 with mitophagy by affecting the deubiquitination of voltage-dependent anion channel 1,a vicious cycle formed by oxidative stress and mitochondrial damage,imbalance of mitochondrial quality control,and tissue-specific susceptibility of apoptotic pathways.In-depth study of these mechanisms is of great significance for the development of therapeutic strategies.Future multi-dimensional target research focusing on mitochondrial protection and metabolic regulation may provide new translational directions for the treatment of SCA3.This article reviews the research progress on the role and underlying mechanisms of mitochondrial dysfunction in SC A3.
Keywords：Spinocerebellar ataxia type 3Mitochondrial dysfunctionMechanismAdenosine triphos-phateOxidative stress
Publication Date：2026-04-18
Online Publishing Date：2026-09-14(First online date of this platform, not the publication date of the document)
Pages：5( 616-620 )