Shaping proteostasis at the cellular, tissue, and organismal level.
TLDR
This review by Morimoto and colleagues examines mechanisms by which protein homeostasis (proteostasis) is achieved in multicellular organisms and discusses the implications for health and disease.Abstract:
The proteostasis network (PN) regulates protein synthesis, folding, transport, and degradation to maintain proteome integrity and limit the accumulation of protein aggregates, a hallmark of aging and degenerative diseases. In multicellular organisms, the PN is regulated at the cellular, tissue, and systemic level to ensure organismal health and longevity. Here we review these three layers of PN regulation and examine how they collectively maintain cellular homeostasis, achieve cell type-specific proteomes, and coordinate proteostasis across tissues. A precise understanding of these layers of control has important implications for organismal health and could offer new therapeutic approaches for neurodegenerative diseases and other chronic disorders related to PN dysfunction.read more
Citations
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Pharmacoperones as Novel Therapeutics for Diverse Protein Conformational Diseases.
Ya-Xiong Tao,P. Michael Conn +1 more
TL;DR: This review will comprehensively summarize this exciting area of research, surveying the literature from in vitro studies in cell lines to transgenic animal models and clinical trials in several protein misfolding diseases.
Journal ArticleDOI
BAG3-mediated proteostasis at a glance.
TL;DR: How the co-chaperone B AG3 maintains the proteome by balancing transcription, translation and autophagy, and how impairment or deregulation of BAG3 can cause muscle weakness, neurodegeneration and cancer are discussed.
Journal ArticleDOI
The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.
Grazia R. Tundo,Diego Sbardella,Anna Maria Santoro,Andrea Coletta,Francesco Oddone,Giuseppe Grasso,Danilo Milardi,Pedro Miguel Lacal,Stefano Marini,Roberto Purrello,Grazia Graziani,Massimo Coletta +11 more
TL;DR: This review will summarize the most recent available literature regarding different aspects of proteasome biology, focusing on structure, function and regulation of prote asome in physiological and pathological processes, mostly cancer and neurodegenerative diseases, connecting biochemical features and clinical studies of proteAsome targeting drugs.
Journal ArticleDOI
The Nuclear SUMO-Targeted Ubiquitin Quality Control Network Regulates the Dynamics of Cytoplasmic Stress Granules
TL;DR: It is demonstrated that the SUMO-targeted ubiquitin ligase (StUbL) pathway, which is part of the nuclear proteostasis network, regulates SG dynamics and proposed that it functions as surveillance pathway for aggregation-prone RBPs in the nucleus, thereby linking the nuclear and cytosolic axis of proteotoxic stress response.
Journal ArticleDOI
The heat shock response in neurons and astroglia and its role in neurodegenerative diseases
TL;DR: This review highlights the complexity of heat shock response activation and addresses whether neurons and glia sense and respond to protein misfolding and aggregation associated with neurodegenerative diseases, in particular Huntington’s disease and amyotrophic lateral sclerosis, by inducing a pro-survival heatshock response.
References
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