Search results for "chaperone"

Structural and Dynamic Disturbances Revealed by Molecular Dynamics Simulations Predict the Impact on Function of CCT5 Chaperonin Mutations Associated…

2023

Mutations in genes encoding molecular chaperones, for instance the genes encoding the subunits of the chaperonin CCT (chaperonin containing TCP-1, also known as TRiC), are associated with rare neurodegenerative disorders. Using a classical molecular dynamics approach, we investigated the occurrence of conformational changes and differences in physicochemical properties of the CCT5 mutations His147Arg and Leu224Val associated with a sensory and a motor distal neuropathy, respectively. The apical domain of both variants was substantially but differently affected by the mutations, although these were in other domains. The distribution of hydrogen bonds and electrostatic potentials on the surfa…

Chaperones in disease: quantitative changes in chronic obstructive pulmonary disease (COPD)

2010

Chaperonology: A novel research field for experimental medicine in the XXI century.

2007

Exosomal HSP60 levels and related miRNAs in brain tumors

In cancer, Extracellular Vesicles (EVs), such as exosomes, contribute to tumor progression by regulating local and systemic parameters [1,2]. Since exosomes are released into body fluids, they may be used in nanomedicine as a valuable source of diagnostic biomarkers [3]. The prognosis of brain tumors is poor even after surgical resection followed by post-operatory chemo- and radio-therapies and it is cogent to find innovative treatments. The discovery that molecular chaperones can be determinant factors in tumorigenesis and the increasing understanding of exosomes, particularly in what refers to their release by tumor cells and contents, including chaperones and miRNA, provide elements to d…

The balance of HSPs expression during pregnancy: the role of placenta

2009

Muscle Histopathological Abnormalities in a Patient With a CCT5 Mutation Predicted to Affect the Apical Domain of the Chaperonin Subunit.

2022

Recognition of diseases associated with mutations of the chaperone system genes, e.g., chaperonopathies, is on the rise. Hereditary and clinical aspects are established, but the impact of the mutation on the chaperone molecule and the mechanisms underpinning the tissue abnormalities are not. Here, histological features of skeletal muscle from a patient with a severe, early onset, distal motor neuropathy, carrying a mutation on the CCT5 subunit (MUT) were examined in comparison with normal muscle (CTR). The MUT muscle was considerably modified; atrophy of fibers and disruption of the tissue architecture were prominent, with many fibers in apoptosis. CCT5 was diversely present in the sarcolem…

GENETIC NEUROCHAPERONOPATHIES ASSOCIATED WITH CCT5 AND HSP60 VARIANTS: ANALYSIS OF THEIR MOLECULAR ANATOMY AND POSSIBLE PATHOGENIC IMPLICATIONS

2022

Hsp27 and Hsp60 in human submandibular salivary gland: Quantitative patterns in healthy and cancerous tissues with potential implications for differe…

2021

Tumors of the submandibular salivary gland (SMG) are uncommon but sufficiently frequent for the physician to consider them in routine examinations and for the pathologist to be prepared to differentiate them from other tissue abnormalities. However, scarcity of specimens makes training difficult, a situation compounded by the lack of accepted universal diagnostic guidelines. Furthermore, there is little information on the chaperone system (CS) of the gland, despite the increasing evidence of its participation in carcinogenesis as a biomarker for diagnosis and patient follow up, and in the mechanisms by which the tumor cells thrive. We are investigating this aspect of various tumors, and her…

Chaperonin Hsp60 and Cancer Therapies

2020

The heat shock protein 60 (Hsp60) is a chaperonin belonging to the chaperoning (chaperone) system that typically contributes to protein homeostasis inside mitochondria, but also plays various non-canonical roles unrelated to protein quality control beyond the organelle. Chaperonopathies are disorders in which chaperones play an etiologic-pathogenic role and contribute to the onset/progression of disease. Hsp60 chaperonopathies by mistake are diseases in which the chaperonin is apparently normal (as far as it can be determined with current methodologies) but it actively contributes to pathology, for example in certain types of cancer, and autoimmune and chronic inflammatory disorders. In cer…

HSP-MOLECULAR CHAPERONES IN CANCER BIOGENESIS AND TUMOR THERAPY: AN OVERVIEW

2012

Molecular chaperones, many of which are heat-shock proteins (HSPs), are an important class of molecules with various functions. Pathological conditions in which chaperones become etiological and/or pathogenic factors are called chaperonopathies, and are classified into by defect, by excess, and by "mistake". In the latter case, the chaperone is structurally and functionally normal but paqrtecipates in pathwais that favor diseases, aòlthough in some cases the chaperone may have post-translational modifications that may lead it to change its location and function and, thus, to become pathogenic. For example, HSP-chaperones are involved in acrcinogenesis in various ways, so that some forms of …