Nature Communications (Feb 2017)
mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases
- 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
Affiliations
- Michela Palmieri
- Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital
- Rituraj Pal
- Department of Molecular Physiology and Biophysics, Baylor College of Medicine
- Hemanth R. Nelvagal
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London
- Parisa Lotfi
- Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital
- Gary R. Stinnett
- Department of Molecular Physiology and Biophysics, Baylor College of Medicine
- Michelle L. Seymour
- Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine
- Arindam Chaudhury
- Department of Molecular Physiology and Biophysics, Dan L. Duncan Cancer Center, Baylor College of Medicine
- Lakshya Bajaj
- Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital
- Vitaliy V. Bondar
- Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital
- Laura Bremner
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London
- Usama Saleem
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London
- Dennis Y. Tse
- Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine
- Deepthi Sanagasetti
- Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital
- Samuel M. Wu
- Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine
- Joel R. Neilson
- Department of Molecular Physiology and Biophysics, Dan L. Duncan Cancer Center, Baylor College of Medicine
- Fred A. Pereira
- Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine
- Robia G. Pautler
- Department of Molecular Physiology and Biophysics, Baylor College of Medicine
- George G. Rodney
- Department of Molecular Physiology and Biophysics, Baylor College of Medicine
- Jonathan D. Cooper
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London
- Marco Sardiello
- Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital
- DOI
- https://doi.org/10.1038/ncomms14338
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 19
Abstract
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.
