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Cited by 158

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Small Molecule Enhancers of Rapamycin-Induced TOR Inhibition Promote Autophagy, Reduce Toxicity in Huntington’s Disease Models and Enhance Killing of Mycobacteria by Macrophages

Open access
Floto, R. Andres, Sarkar, Sovan, Perlstein, Ethan O., Kampmann, Beate, Schreiber, Stuart L., Rubinsztein, David C.·2007·Autophagy

Abstract

Upregulation of autophagy may have therapeutic benefit in a range of diseases that includes neurodegenerative conditions caused by intracytosolic aggregate-prone proteins, such as Huntington's disease, and certain infectious diseases, such as tuberculosis. The best-characterized drug that enhances autophagy is rapamycin, an inhibitor of the TOR (target of rapamycin) proteins, which are widely conserved from yeast to man. Unfortunately, the side effects of rapamycin, especially immunosuppression, preclude its use in treating certain diseases including tuberculosis, which accounts for approximately 2 million deaths worldwide each year, spurring interest in finding novel drugs that selectively enhance autophagy. We have recently reported a novel two-step screening process for the discovery of such compounds. We first identified compounds that enhance the growth-inhibitory effects of rapamycin in the budding yeast Saccharomyces cerevisiae, which we termed small molecule enhancers of rapamycin (SMERs). Next we showed that three SMERs induced autophagy independently, or downstream of mTOR, in mammalian cells, and furthermore enhanced the clearance of a mutant huntingtin fragment in Huntington's disease cell models. These SMERs also protected against mutant huntingtin fragment toxicity in Drosophila. We have subsequently tested two of the SMERs in models of tuberculosis and both enhance the killing of mycobacteria by primary human macrophages.

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Crossref · 10.4161/auto.4898

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Metadata

Authors
Floto, R. A., Sarkar, S., Perlstein, E. O., Kampmann, B., Schreiber, S. L., & Rubinsztein, D. C.
Venue
Autophagy
Published
2007-11-26
Volume
3
Issue
6
Pages
620-622
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
OpenAlex
W2042254284
Cited by
158
References
6
FWCI
5.65
Type
journal article
Language
en
Open access
hybrid

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