mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases

oleh: Michela Palmieri, Rituraj Pal, Hemanth R. Nelvagal, Parisa Lotfi, Gary R. Stinnett, Michelle L. Seymour, Arindam Chaudhury, Lakshya Bajaj, Vitaliy V. Bondar, Laura Bremner, Usama Saleem, Dennis Y. Tse, Deepthi Sanagasetti, Samuel M. Wu, Joel R. Neilson, Fred A. Pereira, Robia G. Pautler, George G. Rodney, Jonathan D. Cooper, Marco Sardiello

Format: Article
Diterbitkan: Nature Portfolio 2017-02-01

Deskripsi

The transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis. Here authors show that trehalose, an mTOR-independent autophagy inducer, alleviates the pathological phenotypes in a mouse model of neurodegenerative disease. Trehalose acts by inhibiting Akt, which normally suppresses TFEB via an mTORC1-independent mechanism.