An Overview of the Role of Molecular Chaperones in Protein Homeostasis

2011 ◽  
Vol 18 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Ana O. Tiroli-Cepeda ◽  
Carlos H.I. Ramos
Keyword(s):  
Molecular Chaperones ◽  
Protein Homeostasis

scholarly journals Functions and Therapeutic Potential of Extracellular Hsp60, Hsp70, and Hsp90 in Neuroinflammatory Disorders

2021 ◽  
Vol 11 (2) ◽  
pp. 736
Author(s):  
Giusi Alberti ◽  
Letizia Paladino ◽  
Alessandra Maria Vitale ◽  
Celeste Caruso Bavisotto ◽  
Everly Conway de Macario ◽  
...  
Keyword(s):  
Molecular Chaperones ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Ubiquitin Proteasome System ◽  
Protein Homeostasis ◽  
Canonical Function ◽  
Cytoprotective Activity ◽  
Ubiquitin Proteasome ◽  
Chaperone Mediated Autophagy

Neuroinflammation is implicated in central nervous system (CNS) diseases, but the molecular mechanisms involved are poorly understood. Progress may be accelerated by developing a comprehensive view of the pathogenesis of CNS disorders, including the immune and the chaperone systems (IS and CS). The latter consists of the molecular chaperones; cochaperones; and chaperone cofactors, interactors, and receptors of an organism and its main collaborators in maintaining protein homeostasis (canonical function) are the ubiquitin–proteasome system and chaperone-mediated autophagy. The CS has also noncanonical functions, for instance, modulation of the IS with induction of proinflammatory cytokines. This deserves investigation because it may be at the core of neuroinflammation, and elucidation of its mechanism will open roads toward developing efficacious treatments centered on molecular chaperones (i.e., chaperonotherapy). Here, we discuss information available on the role of three members of the CS—heat shock protein (Hsp)60, Hsp70, and Hsp90—in IS modulation and neuroinflammation. These three chaperones occur intra- and extracellularly, with the latter being the most likely involved in neuroinflammation because they can interact with the IS. We discuss some of the interactions, their consequences, and the molecules involved but many aspects are still incompletely elucidated, and we hope that this review will encourage research based on the data presented to pave the way for the development of chaperonotherapy. This may consist of blocking a chaperone that promotes destructive neuroinflammation or replacing or boosting a defective chaperone with cytoprotective activity against neurodegeneration.

scholarly journals DNAJ Proteins in neurodegeneration: essential and protective factors

2017 ◽  
Vol 373 (1738) ◽  
pp. 20160534 ◽  
Author(s):  
Christina Zarouchlioti ◽  
David A. Parfitt ◽  
Wenwen Li ◽  
Lauren M. Gittings ◽  
Michael E. Cheetham
Keyword(s):  
Quality Control ◽  
Neurodegenerative Diseases ◽  
Conformational Changes ◽  
Molecular Chaperones ◽  
Protein Quality ◽  
Misfolded Proteins ◽  
Protein Homeostasis ◽  
Polyglutamine Expansion ◽  
Binding Domains

Maintenance of protein homeostasis is vitally important in post-mitotic cells, particularly neurons. Neurodegenerative diseases such as polyglutamine expansion disorders—like Huntington's disease or spinocerebellar ataxia (SCA), Alzheimer's disease, fronto-temporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease—are often characterized by the presence of inclusions of aggregated protein. Neurons contain complex protein networks dedicated to protein quality control and maintaining protein homeostasis, or proteostasis. Molecular chaperones are a class of proteins with prominent roles in maintaining proteostasis, which act to bind and shield hydrophobic regions of nascent or misfolded proteins while allowing correct folding, conformational changes and enabling quality control. There are many different families of molecular chaperones with multiple functions in proteostasis. The DNAJ family of molecular chaperones is the largest chaperone family and is defined by the J-domain, which regulates the function of HSP70 chaperones. DNAJ proteins can also have multiple other protein domains such as ubiquitin-interacting motifs or clathrin-binding domains leading to diverse and specific roles in the cell, including targeting client proteins for degradation via the proteasome, chaperone-mediated autophagy and uncoating clathrin-coated vesicles. DNAJ proteins can also contain ER-signal peptides or mitochondrial leader sequences, targeting them to specific organelles in the cell. In this review, we discuss the multiple roles of DNAJ proteins and in particular focus on the role of DNAJ proteins in protecting against neurodegenerative diseases caused by misfolded proteins. We also discuss the role of DNAJ proteins as direct causes of inherited neurodegeneration via mutations in DNAJ family genes. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

scholarly journals Possible Role of Peroxynitrite in the Responses Induced by Fusicoccin in Plant Cultured Cells

Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 182 ◽  
Author(s):  
Massimo Malerba ◽  
Raffaella Cerana
Keyword(s):  
Cytochrome C ◽  
Dna Fragmentation ◽  
Stress Responses ◽  
Molecular Chaperones ◽  
Caspase 3 ◽  
Cultured Cells ◽  
Acer Pseudoplatanus ◽  
Cytochrome C Release ◽  
Induced Stress

Fusicoccin (FC) is a well-known phytotoxin able to induce in Acer pseudoplatanus L. (sycamore) cultured cells, a set of responses similar to those induced by stress conditions. In this work, the possible involvement of peroxynitrite (ONOO−) in FC-induced stress responses was studied measuring both in the presence and in the absence of 2,6,8-trihydroxypurine (urate), a specific ONOO− scavenger: (1) cell death; (2) specific DNA fragmentation; (3) lipid peroxidation; (4) production of RNS and ROS; (5) activity of caspase-3-like proteases; and (6) release of cytochrome c from mitochondria, variations in the levels of molecular chaperones Hsp90 in the mitochondria and Hsp70 BiP in the endoplasmic reticulum (ER), and of regulatory 14-3-3 proteins in the cytosol. The obtained results indicate a role for ONOO− in the FC-induced responses. In particular, ONOO− seems involved in a PCD form showing apoptotic features such as specific DNA fragmentation, caspase-3-like protease activity, and cytochrome c release from mitochondria.

scholarly journals Adenofection: A Method for Studying the Role of Molecular Chaperones in Cellular Morphodynamics by Depletion-Rescue Experiments

10.3791/54557 ◽  
2016 ◽  
Author(s):  
Margit Fuchs ◽  
Marie-Chloé Boulanger ◽  
Herman Lambert ◽  
Jacques Landry ◽  
Josée N. Lavoie
Keyword(s):  
Molecular Chaperones

scholarly journals Teasing Apart the Role of the Ribosome and Molecular Chaperones in Cellular Protein Folding

2018 ◽  
Vol 114 (3) ◽  
pp. 414a
Author(s):  
Rayna M. Addabbo ◽  
Matthew D. Dalphin ◽  
Yue Liu ◽  
Miranda F. Mecha ◽  
Silvia Cavagnero
Keyword(s):  
Protein Folding ◽  
Molecular Chaperones ◽  
Cellular Protein

scholarly journals Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing

2022 ◽  
Vol 23 (2) ◽  
pp. 649
Author(s):  
Siarhei A. Dabravolski ◽  
Vasily N. Sukhorukov ◽  
Vladislav A. Kalmykov ◽  
Nikolay A. Orekhov ◽  
Andrey V. Grechko ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Chaperones ◽  
Heat Shock Protein 90 ◽  
Misfolded Proteins ◽  
Heart Cells ◽  
Metabolic Demand ◽  
Heart Protection ◽  
High Metabolic Demand

Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.

Molecular cloning and differential expression of sHSP gene family members from the resurrection plant Boea hygrometrica in response to abiotic stresses

Biologia ◽  
2013 ◽  
Vol 68 (4) ◽  
Author(s):  
Zhennan Zhang ◽  
Bo Wang ◽  
Dongmei Sun ◽  
Xin Deng
Keyword(s):  
Molecular Chaperones ◽  
Abiotic Stresses ◽  
Potential Role ◽  
Resurrection Plant ◽  
High Calcium ◽  
Shsp Gene ◽  
Alkaline Conditions ◽  
Boea Hygrometrica ◽  
Shock Proteins

AbstractSmall heat shock proteins (sHSPs) are a class of molecular chaperones that bind to and prevent aggregation of proteins. To assess the potential role of sHSPs in protection against abiotic stresses, we conducted a screening of sHSP genes from the desiccation-tolerant resurrection plant Boea hygrometrica, which is widespread in East Asia in alkaline, calcium-rich limestone crevices. In total, 25 sHSP genes, belonging to six subgroups, were identified from the desiccated leaves of B. hygrometrica. Ten of these genes were cloned and named according to the nomenclature proposed for sHSPs. Transcripts of all these BhsHSPs were detectable in fresh leaves, but only 6 genes were induced after desiccation, and remained high during rehydration. Four of the cytosol-targeted BhsHSP genes were up-regulated under treatments, such as heat, cold, alkaline conditions, high calcium, oxidation, or application of the phytohormone abscisic acid. Together, these results demonstrate that CI and CII sHSPs, especially Bh17.9CI and Bh17.4BCII, are associated with abiotic stresses, and may function in the maintenance of protein stability, aiding in the adaptations to extreme environmental conditions in which B. hygrometrica can survive.

scholarly journals RNAi-Mediated Reverse Genetic Screen Identified Drosophila Chaperones Regulating Eye and Neuromuscular Junction Morphology

2017 ◽  
Vol 7 (7) ◽  
pp. 2023-2038 ◽  
Author(s):  
Sandeep Raut ◽  
Bhagaban Mallik ◽  
Arpan Parichha ◽  
Valsakumar Amrutha ◽  
Chandan Sahi ◽  
...  
Keyword(s):  
Molecular Chaperones ◽  
Bioinformatics Analysis ◽  
Reverse Genetic ◽  
Unfolded Proteins ◽  
Neuronal Function ◽  
Synapse Loss ◽  
Functional Relevance ◽  
Reverse Genetic Screen ◽  
Behavioral Assays

Abstract Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that ∼50% of the chaperones are essential in Drosophila. Knocking down these genes in eyes revealed that ∼30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry, and robust behavioral assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data present the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified a new set of chaperones that regulate eye and NMJ morphogenesis. The outcome of the screen reported here provides a useful resource for further elucidating the role of individual chaperones in Drosophila eye morphogenesis and synaptic development.

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