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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Subcellular localization of the J-protein Sis1 regulates the heat shock response.
Zoë A. Feder,Asif Ali,Abhyudai Singh,Joanna Krakowiak,Xu Zheng,Xu Zheng,Vytas P. Bindokas,Donald Wolfgeher,Stephen J. Kron,David Pincus,David Pincus +10 more
TL;DR: It is revealed that spatial regulation is built into the heat shock response (HSR) in budding yeast and releases the transcription factor Hsf1 from Hsp70-mediated repression to activate the HSR.
Journal ArticleDOI
Systems biology and gene networks in Alzheimer's disease.
TL;DR: Many advantages of the high‐throughput molecular, integrative and network methods used in systems biology studies of AD are presented, which may provide a good reference for future studies employing network biology approaches and large datasets.
Journal ArticleDOI
Silencing of the Hsp70-specific nucleotide-exchange factor BAG3 corrects the F508del-CFTR variant by restoring autophagy
Darren M. Hutt,Sanjay K. Mishra,Daniela Martino Roth,Mads Breum Larsen,Frederic Angles,Raymond A. Frizzell,William E. Balch +6 more
TL;DR: The siRNA-mediated silencing of BAG1 and -3, two BAG members linked to the clearance of misfolded proteins via the UPS and autophagy pathways, leads to functional correction of F508del-CFTR and other disease-associated CFTR variants.
Journal ArticleDOI
Biological Aging and the Cellular Pathogenesis of Huntington's Disease.
TL;DR: The overlap between the hallmarks of aging and HD is reviewed and how aging may contribute to pathogenesis in HD is discussed, suggesting an active role for the aging process in the onset and progression of HD.
Journal ArticleDOI
Cellular Aging Characteristics and Their Association with Age-Related Disorders
Magdalena Rudzińska,Alessandro Parodi,Anastasia V. Balakireva,Olga E. Chepikova,Franco M. Venanzi,Andrey A. Zamyatnin,Andrey A. Zamyatnin +6 more
TL;DR: The role and dysregulation of the molecular pathways controlling cell metabolism and proteostasis, the complexity of the mechanisms that occur during aging, and their association with various age-related disorders are emphasized.
References
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