Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Werner syndrome (WS), caused by mutations at the WRN helicase gene, is a progeroid syndrome characterized by multiple features consistent with accelerated aging. Aberrant double-strand DNA damage repair leads to genomic instability and reduced replicative lifespan of somatic cells. We observed increased autophagy in WRN knockdown cells; this was further increased by short-term rapamycin treatment. Long-term rapamycin treatment resulted in improved growth rate, reduced accumulation of DNA damage foci and improved nuclear morphology; autophagy markers were reduced to near-normal levels, possibly due to clearance of damaged proteins. These data suggest that protein aggregation plays a role in the development of WS phenotypes and that the mammalian target of rapamycin complex 1 pathway is a potential therapeutic target of WS.
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PMID:Rapamycin decreases DNA damage accumulation and enhances cell growth of WRN-deficient human fibroblasts. 2430 46

The mammalian target of rapamycin (mTOR) pathway is an highly conserved signal transduction axis involved in many cellular processes, such as cell growth, survival, transcription, translation, apoptosis, metabolism, motility and autophagy. Recently, this signalling pathway has come to the attention of the scientific community owing to the unexpected finding that inhibition of mTOR by rapamycin, an antibiotic with immunosuppressant and chemotherapeutic properties, extends lifespan in diverse animal models. Moreover, rapamycin has been reported to rescue the cellular phenotype in a progeroid syndrome [Hutchinson-Gilford Progeria syndrome (HGPS)] that recapitulates most of the traits of physiological ageing. The promising perspectives raised by these results warrant a better understanding of mTOR signalling and the potential applications of mTOR inhibitors to counteract ageing-associated diseases and increase longevity. This review is focused on these issues.
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PMID:Potential therapeutic effects of the MTOR inhibitors for preventing ageing and progeria-related disorders. 2695 63