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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Defective Gating and Proteostasis of Human ClC-1 Chloride Channel: Molecular Pathophysiology of Myotonia Congenita
Chung Jiuan Jeng,Ssu Ju Fu,Ssu Ju Fu,Chia Ying You,Yi Jheng Peng,Cheng Tsung Hsiao,Tsung-Yu Chen,Chih Yung Tang +7 more
TL;DR: Elucidation of the molecular structures of human ClC-1 and several CLC homologs provides important insight to the gating and ion permeation mechanisms of this chloride channel, and emerging evidence indicates that the effects of some mutations may entail impaired Cl C-1 protein homeostasis (proteostasis).
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Dietary restriction and gonadal signaling differentially regulate post-development quality control functions in Caenorhabditis elegans
TL;DR: The data suggest that the functional mode of cellular quality control networks can be differentially remodeled, affecting an organism's ability to respond to acute and chronic stresses during adulthood.
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Pervasive convergent evolution and extreme phenotypes define chaperone requirements of protein homeostasis.
TL;DR: By performing a large-scale comparative genomics study of protein homeostasis in 216 eukaryotes, it is found that the relative size of organisms’ chaperone networks, the core components of cellular proteinHomeostasis, directly links to species longevity.
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Inefficient quality control of ribosome stalling during APP synthesis generates CAT-tailed species that precipitate hallmarks of Alzheimer’s disease
Suman Rimal,Yu Li,Rasika Vartak,Ji Geng,Ishaq Tantray,Shuangxi Li,Sungun Huh,Hannes Vogel,Charles G. Glabe,Lea T. Grinberg,Salvatore Spina,William W. Seeley,Su Guo,Bingwei Lu +13 more
TL;DR: In this paper, the ribosomes stall at the ER membrane during co-translational translocation of APP.C99, activating Ribosome-associated quality control (RQC) to resolve ribosome collision and stalled translation.
Journal ArticleDOI
Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system.
Alexander Bolaender,Danuta Zatorska,Huazhong He,Suhasini Joshi,Sahil Sharma,Chander Singh Digwal,Hardik J. Patel,Weilin Sun,Brandon S Imber,Stefan O. Ochiana,Maulik R. Patel,Liza Shrestha,Smit K. Shah,Shuo Wang,Rashad R. Karimov,Hui Tao,Pallav D. Patel,Ananda Rodilla Martin,Pengrong Yan,Palak Panchal,Justina Almodovar,Adriana D. Corben,Andreas Rimner,Stephen D. Ginsberg,Serge K. Lyashchenko,Eva Burnazi,Anson Ku,Teja Kalidindi,Sang-gyu Lee,Milan Grkovski,Bradley J. Beattie,Pat Zanzonico,Jason S. Lewis,Jason S. Lewis,Steve Larson,Anna Rodina,Nagavarakishore Pillarsetty,Viviane Tabar,Mark Dunphy,Tony Taldone,Fumiko Shimizu,Fumiko Shimizu,Gabriela Chiosis,Gabriela Chiosis +43 more
TL;DR: In this article, structural, biochemical, and functional insights into the discovery of epichaperome probes, with a focus on their use in central nervous system diseases, are provided.
References
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