Search results for "chaperonopathies"
showing 10 items of 29 documents
Alzheimer's Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy
2016
Background: Alzheimer’s disease (AD) is a dementia, a neurodegenerative condition, and a protein-misfolding disease or proteinopathy, characterized by protein deposits, extracellular plaques and intracellular neurofibrillary tangles, which contain the AD’s typical pathological proteins, abnormal [1]-amyloid and hyperphosphorylated tau, respectively, and are located predominantly in the cortex of the frontal, parietal, and temporal brain lobes. What is the role of molecular chaperones in AD? Data indicate that molecular chaperones, also known as Hsp, are involved in AD, probably displaying protective roles and/or acting as pathogenic factors as it occurs in chaperonopathies in which case AD …
Chaperonin of Group I: Oligomeric spectrum and biochemical and biological implications
2018
Chaperonins play various physiological roles and can also be pathogenic. Elucidation of their structure, e.g., oligomeric status and post-translational modifications (PTM), is necessary to understand their functions and mechanisms of action in health and disease. Group I chaperonins form tetradecamers with two stacked heptameric rings. The tetradecamer is considered the typical functional complex for folding of client polypeptides. However, other forms such as the monomer and oligomers with smaller number of subunits than the classical tetradecamer, also occur in cells. The properties and functions of the monomer and oligomers, and their roles in chaperonin-associated diseases are still inc…
Missense Mutations of Human Hsp60: A Computational Analysis to Unveil Their Pathological Significance
2020
Two chaperonopathies have been linked to mutations in the human hsp60 (hHsp60; HSPD1) gene, but other existing variants might cause diseases, even if there is no comprehensive information about this possibility. To fill this vacuum, which might be at the basis of misdiagnoses or simply ignorance of chaperonopathies in patients who would benefit by proper identification of their ailments, we searched the sequenced human genomes available in public databases to determine the range of missense mutations in the single hsp60 gene. A total of 224 missense mutations were identified, including those already characterized. Detailed examination of these mutations was carried out to assess their possi…
The neurochaperonopathies: Anomalies of the chaperone system with pathogenic effects in neurodegenerative and neuromuscular disorders
2021
The chaperone (or chaperoning) system (CS) constitutes molecular chaperones, co-chaperones, and chaperone co-factors, interactors and receptors, and its canonical role is protein quality control. A malfunction of the CS may cause diseases, known as the chaperonopathies. These are caused by qualitatively and/or quantitatively abnormal molecular chaperones. Since the CS is ubiquitous, chaperonopathies are systemic, affecting various tissues and organs, playing an etiologic-pathogenic role in diverse conditions. In this review, we focus on chaperonopathies involved in the pathogenic mechanisms of diseases of the central and peripheral nervous systems: the neurochaperonopathies (NCPs). Genetic …
Quantitative immunomorphological analysis of heat shock proteins in thyroid follicular adenoma and carcinoma tissues reveals their potential for diff…
2019
Hsp27, Hsp60, Hsp70, and Hsp90 are chaperones that play a crucial role in cellular homeostasis and differentiation, but they may be implicated in carcinogenesis. Follicular neoplasms of the thyroid include follicular adenoma and follicular carcinoma. The former is a very frequent benign encapsulated nodule, whereas the other is a nodule that infiltrates the capsule, blood vessels and the adjacent parenchyma, with a tendency to metastasize. The main objective was to assess the potential of the Hsps in differential diagnosis and carcinogenesis. We quantified by immunohistochemistry Hsp27, Hsp60, Hsp70, and Hsp90 on thin sections of human thyroid tissue with follicular adenoma or follicular ca…
Quantitative analysis of the impact of a human pathogenic mutation on the CCT5 chaperonin subunit using a proxy archaeal ortholog
2017
The human chaperonin complex is a ~ 1 MDa nanomachine composed of two octameric rings formed from eight similar but non-identical subunits called CCT. Here, we are elucidating the mechanism of a heritable CCT5 subunit mutation that causes profound neuropathy in humans. In previous work, we introduced an equivalent mutation in an archaeal chaperonin that assembles into two octameric rings like in humans but in which all subunits are identical. We reported that the hexadecamer formed by the mutant subunit is unstable with impaired chaperoning functions. This study quantifies the loss of structural stability in the hexadecamer due to the pathogenic mutation, using differential scanning calorim…
Functions and Therapeutic Potential of Extracellular Hsp60, Hsp70, and Hsp90 in Neuroinflammatory Disorders
2021
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. …
The Challenging Riddle about the Janus-Type Role of Hsp60 and Related Extracellular Vesicles and miRNAs in Carcinogenesis and the Promises of Its Sol…
2021
Hsp60 is one of the most ancient and evolutionarily conserved members of the chaperoning system. It typically resides within mitochondria, in which it contributes to maintaining the organelle’s proteome integrity and homeostasis. In the last few years, it has been shown that Hsp60 also occurs in other locations, intracellularly and extracellularly, including cytosol, plasma-cell membrane, and extracellular vesicles (EVs). Consequently, non-canonical functions and interacting partners of Hsp60 have been identified and it has been realized that it is a hub molecule in diverse networks and pathways and that it is implicated, directly or indirectly, in the development of various pathological co…
Hsp60 Post-translational Modifications: Functional and Pathological Consequences.
2020
Hsp60 is a chaperone belonging to the Chaperonins of Group I and typically functions inside mitochondria in which, together with the co-chaperonin Hsp10, maintains protein homeostasis. In addition to this canonical role, Hsp60 plays many others beyond the mitochondria, for instance in the cytosol, plasma-cell membrane, extracellular space, and body fluids. These non-canonical functions include participation in inflammation, autoimmunity, carcinogenesis, cell replication, and other cellular events in health and disease. Thus, Hsp60 is a multifaceted molecule with a wide range of cellular and tissue locations and functions, which is noteworthy because there is only one hsp60 gene. The questio…
Hsp60 Friend and Foe of the Nervous System
2019
Hsp60 belongs to the subgroup of molecular chaperones named chaperonins and, typically, resides and functions in the mitochondria but it is also present in extramitochondrial sites. It chaperones client peptides as they fold to achieve the native conformation and also displays anti-stress roles by helping stress-damaged proteins regain a functional shape. Thus, Hsp60 is central to the integrity and functionality of mitochondria and energy production. All cells in the nervous system depend on Hsp60 so when the chaperonin malfunctions the consequences on nervous tissues are usually devastating, causing diverse diseases. These are the Hsp60 chaperonopathies, which can be genetic or acquired wi…