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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 autophagy proteins, attenuated the expression and toxic effects of mutant ataxin-3 on neurons, and alleviated the effects of ataxin-3 on autophagy. Therefore, MSCs are associated with autophagy-inducing therapy and compared to animal models, our MSCs co-culture could be used as a novel and potential therapeutic approach to study SCA3 disease and other neurodegenerative diseases.<\/jats:p>","DOI":"10.1038\/s41419-022-05085-0","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T10:03:01Z","timestamp":1658138581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Transcription factor EB-mediated mesenchymal stem cell therapy induces autophagy and alleviates spinocerebellar ataxia type 3 defects in neuronal cells model"],"prefix":"10.1038","volume":"13","author":[{"given":"Xiaobo","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"de Dieu Habimana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Mukama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyue","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihao","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jufang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-xin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5963-4225","authenticated-orcid":false,"given":"Zhiyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"5085_CR1","doi-asserted-by":"publisher","first-page":"104635","DOI":"10.1016\/j.nbd.2019.104635","volume":"134","author":"HS McLoughlin","year":"2020","unstructured":"McLoughlin HS, Moore LR, Paulson HL. 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