Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

By B. Ravikumar, C. Vacher, Z. Berger, J. Davies, S. Luo, L. Oroz, F. Scaravilli, D. Easton, R. Duden, Cahir O'Kane and 1 more. Nature Genetics, 2004

2,455 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/7fe2ed77fba09e566e702d0c9257ac94fbeaa624

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Citations in the corpus

Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities. (2017, unknown): “…microscopy - the reduction of the large aggregates after autophagy induction may reflect a reduced input of the smaller species into the aggregates and the flux of the mutant proteins on and off the aggregates (Berger et al., 2006; Ravikumar et al., 2002; Ravikumar et al., 2004; Webb et al., 2003).”
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis (2019, background): “Rapamycin, a small molecule inhibitor of mTOR, stimulates autophagy through the formation of autophagosomes from the phagophore and enhances protein degradation (Ravikumar et al., 2004; BacharWikstrom et al., 2013).”
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study (2005, background): “Autophagy, the other major pathway to lysosomes, has received limited attention in relation to AD (25), although its importance as a mechanism for removing defective organelles and potentially toxic proteins (26, 27) and as a determinant of cell survival (28) in various disease settings is becoming ”
Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein (2017, background): “…required for key cellular processes (Kim et al., 2016), including mTOR, which plays key roles in the regulation of autophagy (Tsvetkov et al., 2013; Petersén A et al., 2001; Ravikumar et al., 2004; Pryor et al., 2014; Ashkenazi et al., 2017; Caviston et al., 2007; Wong and Holzbaur, 2014).”
Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease (2010, background): “gy has been implicated in the regulation of amyloid accumulation in vivo[26] and in the clearance of huntingtin[21,40] and asynuclein[41].”
Autophagy gone awry in neurodegenerative diseases (2010, unknown): “In addition, pharmacological upregulation of macroautophagy has been shown effective in reducing neuronal aggregates and slowing the progression of neurological symptoms in fly and mouse models of Huntington's diseas”
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease (2005, background): “Moreover, macroautophagy is involved in degrading mutated and aggregated proteins that are implicated in neurodegenerative diseases, including Parkinson’s (Cuervo et al., 2004) and Huntington’s disease (Ravikumar et al., 2004).”