Abstract:
:In a recent paper we addressed the mechanism by which defective autophagy contributes to TARDBP/TDP-43-mediated neurodegenerative disorders. We demonstrated that TARDBP regulates MTORC1-TFEB signaling by targeting RPTOR/raptor, a key component and an adaptor protein of MTORC1. Loss of TARDBP decreased the mRNA stability of RPTOR and this regulation in turn enhanced autophagosomal and lysosomal biogenesis in an MTORC1-dependent manner. Meanwhile, loss of TARDBP could also impair autophagosome-lysosome fusion in an MTORC1-independent manner. Importantly, we found that modulation of MTOR activity by treatment with rapamycin and phosphatidic acid had strong effects on the neurodegenerative phenotypes of TBPH (Drosophila TARDBP)-depleted flies. Taken together, our data reveal that multiple dysfunctions in the autophagic process contribute to TARDBP-linked neurodegeneration and may help to identify potential therapeutic targets in the future.
journal_name
Autophagyjournal_title
Autophagyauthors
Ying Z,Xia Q,Hao Z,Xu D,Wang M,Wang H,Wang Gdoi
10.1080/15548627.2016.1151596subject
Has Abstractpub_date
2016-01-01 00:00:00pages
707-8issue
4eissn
1554-8627issn
1554-8635journal_volume
12pub_type
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