Journal ArticleDOI
Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system.
TLDR
The UPS and autophagy-mediated tau clearance mechanisms are reviewed and the biochemical connections between these two processes are outlined and pharmacological methods that target these degradation systems for the treatment and prevention of AD are discussed.About:
This article is published in Progress in Neurobiology.The article was published on 2013-06-01. It has received 283 citations till now. The article focuses on the topics: Autophagy & Cognitive decline.read more
Citations
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Journal ArticleDOI
Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies
Aaron Ciechanover,Yong T.ae Kwon +1 more
TL;DR: An overview of the proteolytic pathways in neurons is provided, with an emphasis on the UPS, CMA and macroautophagy, and the role of protein quality control in the degradation of pathogenic proteins in neurodegenerative diseases is discussed.
Journal ArticleDOI
Roles of tau protein in health and disease.
TL;DR: It is important to fully understand the range of neuronal functions attributed to tau, since this will provide vital information on its involvement in the development and pathogenesis of disease, and enable determination of which critical molecular pathways should be targeted by potential therapeutic agents developed for the treatment of tauopathies.
Journal ArticleDOI
The role of protein clearance mechanisms in organismal ageing and age-related diseases
TL;DR: Modulation of either proteasome activity or autophagic-lysosomal potential extends lifespan and protects organisms from symptoms associated with proteostasis disorders, suggesting that protein clearance mechanisms are directly linked to ageing and age-associated diseases.
Journal ArticleDOI
Regulation of proteasome activity in health and disease.
Marion Schmidt,Daniel Finley +1 more
TL;DR: The contributions of the proteasome to human pathology, mechanisms that regulate the proteolytic capacity of the Proteasome are described, and strategies to modulate proteasomes function as a therapeutic approach to ameliorate diseases associated with altered UPS function are discussed.
Journal ArticleDOI
Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling
Natura Myeku,Catherine L. Clelland,Sheina Emrani,Nikolay V. Kukushkin,Wai Haung Yu,Alfred L. Goldberg,Karen Duff +6 more
TL;DR: Administration of an agent that activates cAMP–protein kinase A (PKA) signaling led to attenuation of proteasome dysfunction, probably through proteasomesome subunit phosphorylation in vivo, which led to lower levels of aggregated tau and improvements in cognitive performance.
References
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Journal ArticleDOI
Alzheimer's Disease: Genes, Proteins, and Therapy
TL;DR: Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.
Journal ArticleDOI
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Journal ArticleDOI
Methods in Mammalian Autophagy Research
TL;DR: Methods to monitor autophagy and to modulate autophagic activity are discussed, with a primary focus on mammalian macroautophagy.
Journal ArticleDOI
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
TL;DR: It is clear now that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a variety of basic pathways during cell life and death as well as in health and disease.
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
TL;DR: The results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.
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CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
Leonard Petrucelli,Dennis W. Dickson,Kathryn Kehoe,Julie P. Taylor,Heather Snyder,Andrew Grover,Michael De Lucia,Eileen McGowan,Jada Lewis,G. Prihar,Jungsu Kim,Wolfgang H. Dillmann,Susan E. Browne,Alexis Hall,Richard Voellmy,Yoshio Tsuboi,Ted M. Dawson,Benjamin Wolozin,John Hardy,Mike Hutton +19 more