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
More filters
Journal ArticleDOI
Phytochemical Study and In Vitro Screening Focusing on the Anti-Aging Features of Various Plants of the Greek Flora
Aimilia D. Sklirou,Maria T. Angelopoulou,Aikaterini Argyropoulou,Eliza Chaita,Vasiliki Ioanna Boka,Christina Cheimonidi,Katerina Niforou,Eleni Mavrogonatou,Harris Pratsinis,Eleftherios Kalpoutzakis,Nektarios Aligiannis,Dimitris Kletsas,Ioannis P. Trougakos,Alexios-Leandros Skaltsounis,Alexios-Leandros Skaltsounis +14 more
TL;DR: In this article, an extensive screening among hundreds of plant species and subspecies were selected and evaluated for their antioxidant and anti-melanogenic properties, while the most promising were further subjected to various in vitro and cell-based assays related to skin aging.
Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation - eScholarship
Jason Gestwicki,Adrienne M. Wang,Yoshinari Miyata,Susan Klinedinst,Hwei Ming Peng,Jason P. Chua,Tomoko Komiyama,Xiaokai Li,Yoshihiro Morishima,Diane E. Merry,William B. Pratt +10 more
TL;DR: In this article, the polyglutamine androgen receptor (polyQ AR) was reduced in models of spinobulbar muscular atrophy, a protein aggregation neurodegenerative disorder.
Journal ArticleDOI
Protecting the future: balancing proteostasis for reproduction
TL;DR: In this paper , the authors review recent insights into these different modes of regulation and their implications for reproductive and somatic aging, and reveal multiple layers of PN regulation that support germ cell function, determine reproductive capacity during aging and prioritize reproduction at the expense of somatic health.
Journal ArticleDOI
Targeting retinoic acid receptor alpha-corepressor interaction activates chaperone-mediated autophagy and protects against retinal degeneration
Raquel Gómez-Sintes,Qisheng Xin,Juan Ignacio Jiménez-Loygorri,Mericka McCabe,Antonio Diaz,Thomas P. Garner,Xiomaris M. Cotto-Rios,Yang Wu,Shuxian Dong,Cara A. Reynolds,Bindi Patel,P. De La Villa,Fernando Macian,Patricia Boya,Evripidis Gavathiotis,Ana Maria Cuervo +15 more
TL;DR: In this article , the authors identify the mechanism of action of selective chaperone-mediated autophagy activators previously developed by their group and leveraged that information to generate orally bioavailable chaperones with favorable brain exposure and suggest a therapeutic strategy for retinal degeneration.
Journal ArticleDOI
Thermal stress induces tissue damage and a broad shift in regenerative signaling pathways in the honey bee digestive tract.
Dunay M. Bach,Miriam A. Holzman,Fatoumata Wague,JJ L. Miranda,Allison J. Lopatkin,Allison J. Lopatkin,Jennifer H. Mansfield,Jonathan W. Snow +7 more
TL;DR: In this article, the authors used RNAseq and thermal stress coupled with RNAseq to identify broad transcriptional remodeling of a number of key signaling pathways in the honey bee, including those pathways known to be involved in digestive tract regeneration in the fruit fly such as the Hippo and JAK/STAT pathways.
References
More filters
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.