Journal ArticleDOI
Fighting neurodegeneration with rapamycin: mechanistic insights
TLDR
The molecular mechanisms underlying the neuroprotective effects of rapamycin are reviewed and the therapeutic potential of this compound for neurodegenerative diseases is discussed.Abstract:
A growing number of studies point to rapamycin as a pharmacological compound that is able to provide neuroprotection in several experimental models of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease and spinocerebellar ataxia type 3. In addition, rapamycin exerts strong anti-ageing effects in several species, including mammals. By inhibiting the activity of mammalian target of rapamycin (mTOR), rapamycin influences a variety of essential cellular processes, such as cell growth and proliferation, protein synthesis and autophagy. Here, we review the molecular mechanisms underlying the neuroprotective effects of rapamycin and discuss the therapeutic potential of this compound for neurodegenerative diseases.read more
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Mechanism and medical implications of mammalian autophagy
Ivan Dikic,Zvulun Elazar +1 more
TL;DR: It is now apparent that autophagy is deregulated in the context of various human pathologies, including cancer and neurodegeneration, and its modulation has considerable potential as a therapeutic approach.
Journal ArticleDOI
Ageing as a Risk Factor for Disease
Teresa Niccoli,Linda Partridge +1 more
TL;DR: Lowered activity of the nutrient-sensing insulin/insulin-like growth factor/Target of Rapamycin signalling network can extend healthy lifespan in yeast, multicellular invertebrates, mice and, possibly, humans.
Journal ArticleDOI
The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis
Agnes Roczniak-Ferguson,Constance S. Petit,Florian Froehlich,Sharon Qian,Jennifer Ky,Brittany Angarola,Tobias C. Walther,Shawn M. Ferguson +7 more
TL;DR: TFEB is identified as a target of mTOR and a mechanism for matching the transcriptional regulation of genes encoding proteins of autophagosomes and lysosomes to cellular need is suggested.
Journal ArticleDOI
Rapamycin: one drug, many effects
TL;DR: Rapamycin, a specific inhibitor of mTOR, has been shown to be useful in the treatment of certain diseases and its mechanism of action is discussed and the potential utility of combination therapy with rapamycin is highlighted.
Journal Article
Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization.:II. FERMENTATION, ISOLATION AND CHARACTERIZATION
TL;DR: Rapamycin is a new antifungal antibiotic produced by Streptomyces hygroscopicus and can be classified as a triene, highly active against various Candida species, especially Candida albicans.
References
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Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Journal ArticleDOI
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TL;DR: It is shown that TDP-43 is the major disease protein in both frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis.
PatentDOI
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
TL;DR: In this paper, the rictor-mTOR complex was used to identify compounds which modulate Akt activity mediated by the Rictor mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activation.
Journal ArticleDOI
Parkinson's disease: Mechanisms and models
TL;DR: PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.
Journal ArticleDOI
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Taichi Hara,Kenji Nakamura,Makoto Matsui,Makoto Matsui,Makoto Matsui,Akitsugu Yamamoto,Yohko Nakahara,Rika Suzuki-Migishima,Minesuke Yokoyama,Kenji Mishima,Ichiro Saito,Hideyuki Okano,Noboru Mizushima +12 more
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