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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Journal ArticleDOI
Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor.
Tatiana Tiago,Barbara Hummel,Federica Francesca Morelli,Valentina Basile,Jonathan Vinet,Veronica Galli,Laura Mediani,Francesco Antoniani,Silvia Pomella,Matteo Cassandri,Maria Giovanna Garone,Beatrice Silvestri,Beatrice Silvestri,Marco Cimino,Giovanna Cenacchi,Roberta Costa,Vincent Mouly,Ina Poser,Esti Yeger-Lotem,Alessandro Rosa,Alessandro Rosa,Simon Alberti,Rossella Rota,Anat Ben-Zvi,Ritwick Sawarkar,Ritwick Sawarkar,Serena Carra +26 more
TL;DR: In this article, the lamin B receptor (LBR)-tether was shown to be a specialized chaperone engaged in muscle cell differentiation and that dysfunctional HSPB3 causes neuromuscular disease by deregulating LBR.
Journal ArticleDOI
Natural Products as Modulators of the Proteostasis Machinery: Implications in Neurodegenerative Diseases.
TL;DR: This review will focus on the current knowledge regarding the use of natural products as modulators of different components of the proteostasis machinery within the framework of age-associated neurodegenerative diseases.
Journal ArticleDOI
Modulation of Protein Synthesis by eIF2α Phosphorylation Protects Cell from Heat Stress-Mediated Apoptosis.
TL;DR: It is proposed that transient modulation of protein synthesis by eIF2α phosphorylation has a pivotal role in protecting cells from heat stress-induced apoptosis, and pharmacological agents that promote eIF1αosphorylation or reduce ER stress may contribute to the development of promising therapeutic approaches against heat-related diseases.
Book ChapterDOI
Folding Defects Leading to Primary Hyperoxaluria.
TL;DR: Primary hyperoxalurias can be ranked among protein misfolding disorders, because in most cases the enzymatic deficit is due to the inability of each enzyme to reach its native and functional conformation, and molecules able to improve the folding yield of the enzymes involved in each disease form could represent new therapeutic strategies.
Journal ArticleDOI
Aging: therapeutics for a healthy future
Robert Hodgson,Robert Hodgson,Brian K. Kennedy,Brian K. Kennedy,Eliezer Masliah,Kimberly Scearce-Levie,Barbara Tate,Anjli Venkateswaran,Steven P. Braithwaite +8 more
TL;DR: The need for therapeutics that address aging and age-related disorders is acute, but the promise of effective treatments provides huge opportunities that, as a community, the authors all seek to enable effectively as soon as possible.
References
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Journal ArticleDOI
Tissue-based map of the human proteome
Mathias Uhlén,Mathias Uhlén,Linn Fagerberg,Björn M. Hallström,Cecilia Lindskog,Per Oksvold,Adil Mardinoglu,Åsa Sivertsson,Caroline Kampf,Evelina Sjöstedt,Evelina Sjöstedt,Anna Asplund,IngMarie Olsson,Karolina Edlund,Emma Lundberg,Sanjay Navani,Cristina Al-Khalili Szigyarto,Jacob Odeberg,Dijana Djureinovic,Jenny Ottosson Takanen,Sophia Hober,Tove Alm,Per-Henrik Edqvist,Holger Berling,Hanna Tegel,Jan Mulder,Johan Rockberg,Peter Nilsson,Jochen M. Schwenk,Marica Hamsten,Kalle von Feilitzen,Mattias Forsberg,Lukas Persson,Fredric Johansson,Martin Zwahlen,Gunnar von Heijne,Jens Nielsen,Jens Nielsen,Fredrik Pontén +38 more
TL;DR: In this paper, a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level.
Journal ArticleDOI
The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
Journal ArticleDOI
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
Journal ArticleDOI
An nrf2/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements
Ken Itoh,Tomoki Chiba,Satoru Takahashi,Tetsuro Ishii,Kazuhiko Igarashi,Yasutake Katoh,Tatsuya Oyake,Norio Hayashi,Kimihiko Satoh,Ichiro Hatayama,Masayuki Yamamoto,Yo-ichi Nabeshima +11 more
TL;DR: It is demonstrated that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes and the nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.
Journal ArticleDOI
Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy
Sue C. Bodine,Esther Latres,Susanne Baumhueter,Venus Lai,Lorna Nunez,Brian A. Clarke,William Poueymirou,Frank J. Panaro,Erqian Na,Kumar Dharmarajan,Zhen-Qiang Pan,David M. Valenzuela,Thomas M. DeChiara,Trevor Stitt,George D. Yancopoulos,David J. Glass +15 more
TL;DR: Two genes encode ubiquitin ligases that are potential drug targets for the treatment of muscle atrophy, and mice deficient in either MAFbx orMuRF1 were found to be resistant to atrophy.