Transcription factor EB-mediated mesenchymal stem cell therapy induces autophagy and alleviates spinocerebellar ataxia type 3 defects in neuronal cells model.

ABSTRACT: Defects in ataxin-3 proteins and CAG repeat expansions in its coding gene ATXN3 cause Spinocerebellar Ataxia Type 3 (SCA3) or Machado-Joseph disease (MJD) polyglutamine neurodegenerative disease. The mutant proteins aggregate as inclusion bodies in cells and compete with wild-type ataxin-3, which leads to neuronal dysfunction or death and impairs Beclin1-mediated autophagy. It has been reported that Mesenchymal stem cells (MSCs) can reliably treat several neurodegenerative diseases. Herein, we used a Transcription Factor EB (TFEB) nuclear translocation-mediated MSCs co-culture approach to reconstitute autophagy and lysosomal biogenesis, and reduce SCA3-like behaviors in induced pluripotent stem cells (iPSCs)-derived neuron cells models. Our iPSCs model showed enhanced expression of autopha

SUBMITTER: Han X 

PROVIDER: S-EPMC9293975 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature