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Responses to Muscular Exercise, Heat Shock Proteins as Regulators of Inflammation, and Mitochondrial Quality Control
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Alex T. Von Schulze, Paige C. Geiger
Broadly defined, molecular chaperones are a key set of proteins that help “guide” various proteins within the cell to remain functional and/or get targeted for degradation under stressful conditions. In this way, molecular chaperones such as HSPs allow cells to survive under stress. HSPs specifically facilitate the folding of new proteins, the refolding of damaged proteins, the targeting on non-functional proteins/organelles for degradation, intracellular signalling, and the import/export of proteins into/out of the mitochondria (Figure 7.1) (15, 24, 29, 92). Importantly, different HSPs (characterized by their molecular weight in kilodaltons) have varying functions. For the purposes of this chapter, we will focus on four well-characterized HSP families: HSP70, HSP40, HSP90, and HSP25.
Human Responses to Endotoxin: Role of the Genetic Background
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Heat-shock proteins represent a physiological response to cellular stress, which is highly conserved in evolution. Expression of heat-shock proteins as molecular chaperones facilitates intracellular folding of synthesized proteins (45). Inhibition of the heat-shock response exacerbates septic shock in animal models. On the other hand, induction of heat-shock proteins prior to lethal endotoxin challenges reduces the lethality of septic shock (45).
The Stress Response and Stress Proteins
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Martin E. Feder, Dawn A. Parsell, Susan L. Lindquist
The primary structure of proteins contains all the information needed for acquisition of native structure, and many isolated polypeptides can fold correctly to achieve native structure in vitro. Molecular chaperones impart no steric information to their target proteins; chaperones simply facilitate the self-directed folding process. Nonetheless, molecular chaperones are extremely important, and a brief consideration of protein folding may clarify why this is so.
Role of curcumin and its nanoformulations in the treatment of neurological diseases through the effects on stem cells
Published in Journal of Drug Targeting, 2023
Nasim Sabouni, Hadi Zare Marzouni, Sepideh Palizban, Sepideh Meidaninikjeh, Prashant Kesharwani, Tannaz Jamialahmadi, Amirhossein Sahebkar
Regarding the molecular mechanisms of the hormesis effect, a connection has been assumed between modulating redox status and vitagenes-related neuroprotection [80]. Nowadays, we know that some molecular chaperones must maintain homeostasis by disrupting the aggregate and preventing protein misfolding. Nonetheless, during multiple diseases such as cancer, metabolic diseases, and neurodegenerative disorders in which chronic oxidative stress is soaring to an uncontrolled level, the repair system, including vitagenes, begins to function [63]. Vitagenes are protective genes involved in restoring hemostasis during the oxidative stress-induced condition. Therefore, they are effective agents for controlling ageing. These genes encode for Hsp32, Hsp70, heat shock proteins (Hsp), sirtuin protein system, and thioredoxin, and their activity reduces mitochondrial ROS production [81]. Recently, herbal extracts such as natural polyphenols have been neuroprotective via activating vitagenes as the hormetic pathways [82, 83]. Recent findings have revealed that one of the intracellular systems affected by curcumin and its metabolites is members of the vitagenes family, such as HSP70. Indeed, stimulation of vitagenes by curcumin results in modulating the redox system that consequently causes an antioxidant effect in a dose-dependent manner. Hence, this property can be an excellent optional therapy for age-related neurological disorders [84, 85].
Design, synthesis, biological evaluation and molecular docking study of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as novel HSP90 N-terminal inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Man Yang, Chenyao Li, Yajing Li, Chen Cheng, Meiyun Shi, Lei Yin, Hongyu Xue, Yajun Liu
Because proteins play roles in nearly every cellular process, it is essential to maintain protein homeostasis to preserve normal cell functions. Molecular chaperones are a large family of proteins that guard cellular protein homeostasis by regulating the conformation and quality of client proteins1,2. Heat shock protein 90 (HSP90) is one of the most crucial molecular chaperones in eukaryotes and stabilises and activates more than 400 client proteins3,4. Because cancer cells require higher levels of proteins for survival than normal cells, HSP90 is overexpressed in cancer cells, accounting for 4–6% of the whole proteome5,6. In addition, conformations of normal HSP90 and HSP90 of the cancer phenotype are different, and the latter is more susceptible to inhibitors7. Inhibition of HSP90 in cancer cells results in the degradation of client oncoproteins via the ubiquitin-proteasome pathway and the subsequent disruption of multiple signal transduction pathways, further leading to the apoptosis of cancer cells8,9. Therefore, HSP90 is a promising therapeutic target for discovering anticancer drugs10. Beyond cancer, HSP90 has also emerged as a potential drug target in other protein-related diseases, such as neurodegenerative diseases, infectious diseases, and ageing11–14.
BRICHOS: a chaperone with different activities depending on quaternary structure and cellular location?
Published in Amyloid, 2019
Axel Leppert, Gefei Chen, Jan Johansson
Protein homeostasis (proteostasis) is achieved by controlling the concentration, conformation, binding partners and localization of proteins from synthesis to degradation. Molecular chaperones are key players in the proteostasis network, and help to maintain cellular viability by promoting protein folding into native states over aggregation, but also fulfil other functions [1]. Many currently untreatable human diseases are associated with extracellular deposits of specific misfolded and aggregated proteins, for instance amyloid-β peptide (Aβ) in Alzheimer disease (AD), islet amyloid polypeptide (IAPP) in Type II diabetes, or surfactant protein C (SP-C) in interstitial lung disease [2,3]. Most characterized molecular chaperones participate in intracellular networks, with unclear relevance for extracellular protein aggregation, and the roles of extracellular chaperones thus need to be investigated in more detail.