Title |
Modulation of mTOR signaling as a strategy for the treatment of Pompe disease
|
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Published in |
EMBO Molecular Medicine, January 2017
|
DOI | 10.15252/emmm.201606547 |
Pubmed ID | |
Authors |
Jeong‐A Lim, Lishu Li, Orian S Shirihai, Kyle M Trudeau, Rosa Puertollano, Nina Raben |
Abstract |
Mechanistic target of rapamycin (mTOR) coordinates biosynthetic and catabolic processes in response to multiple extracellular and intracellular signals including growth factors and nutrients. This serine/threonine kinase has long been known as a critical regulator of muscle mass. The recent finding that the decision regarding its activation/inactivation takes place at the lysosome undeniably brings mTOR into the field of lysosomal storage diseases. In this study, we have examined the involvement of the mTOR pathway in the pathophysiology of a severe muscle wasting condition, Pompe disease, caused by excessive accumulation of lysosomal glycogen. Here, we report the dysregulation of mTOR signaling in the diseased muscle cells, and we focus on potential sites for therapeutic intervention. Reactivation of mTOR in the whole muscle of Pompe mice by TSC knockdown resulted in the reversal of atrophy and a striking removal of autophagic buildup. Of particular interest, we found that the aberrant mTOR signaling can be reversed by arginine. This finding can be translated into the clinic and may become a paradigm for targeted therapy in lysosomal, metabolic, and neuromuscular diseases. |
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Spain | 2 | 22% |
United States | 2 | 22% |
Germany | 1 | 11% |
Brazil | 1 | 11% |
Unknown | 3 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 6 | 67% |
Practitioners (doctors, other healthcare professionals) | 1 | 11% |
Science communicators (journalists, bloggers, editors) | 1 | 11% |
Scientists | 1 | 11% |
Mendeley readers
Geographical breakdown
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United States | 1 | <1% |
Unknown | 112 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 30 | 27% |
Researcher | 20 | 18% |
Student > Bachelor | 15 | 13% |
Student > Master | 14 | 12% |
Student > Doctoral Student | 4 | 4% |
Other | 11 | 10% |
Unknown | 19 | 17% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 21 | 19% |
Medicine and Dentistry | 11 | 10% |
Neuroscience | 7 | 6% |
Immunology and Microbiology | 3 | 3% |
Other | 9 | 8% |
Unknown | 23 | 20% |