Show simple item record

dc.contributor.authorMacario, A.J.L.
dc.contributor.authorde Macario, E.C.
dc.date.accessioned2019-12-04T15:55:06Z
dc.date.available2019-12-04T15:55:06Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85075440577&doi=10.1002%2fpath.5349&partnerID=40&md5=a25b8aa4337d14c0a7a5ce4df31b36bf
dc.identifier.urihttp://hdl.handle.net/10713/11483
dc.description.abstractMolecular chaperones, many of which are heat shock proteins (Hsps), are components of the chaperoning system and when defective can cause disease, the chaperonopathies. Chaperone-gene variants cause genetic chaperonopathies, whereas in the acquired chaperonopathies the genes are normal, but their protein products are not, due to aberrant post-transcriptional mechanisms, e.g. post-translational modifications (PTMs). Since the chaperoning system is widespread in the body, chaperonopathies affect various tissues and organs, making these diseases of interest to a wide range of medical specialties. Genetic chaperonopathies are uncommon but the acquired ones are frequent, encompassing various types of cancer, and inflammatory and autoimmune disorders. The clinical picture of chaperonopathies is known. Much less is known on the impact that pathogenic mutations and PTMs have on the properties and functions of chaperone molecules. Elucidation of these molecular alterations is necessary for understanding the mechanisms underpinning the tissue and organ abnormalities occurring in patients. To illustrate this issue, we discuss structural-functional alterations caused by mutation in the chaperones CCT5 and HSPA9, and PTM effects on Hsp60. The data provide insights into what may happen when CCT5 and HSPA9 malfunction in patients, e.g. accumulation of cytotoxic protein aggregates with tissue destruction; or for Hsp60 with aberrant PTM, degradation and/or secretion of the chaperonin with mitochondrial damage. These and other possibilities are now open for investigation.en_US
dc.description.sponsorshipAJLM and ECdeM were partially supported by IMET and IEMEST. This is IMET contribution number IMET 19?015.en_US
dc.description.urihttps://doi.org/10.1002/path.5349en_US
dc.language.isoen_USen_US
dc.publisherJohn Wiley and Sons Ltden_US
dc.relation.ispartofJournal of Pathology
dc.subjectCCTen_US
dc.subjectchaperoninsen_US
dc.subjectchaperonopathiesen_US
dc.subjectHspen_US
dc.subjectHsp60en_US
dc.subjectHsp70en_US
dc.subjectmolecular chaperonesen_US
dc.subjectmutationen_US
dc.subjectoligomeren_US
dc.subjectpost-translational modificationen_US
dc.titleMolecular mechanisms in chaperonopathies: clues to understanding the histopathological abnormalities and developing novel therapiesen_US
dc.typeArticleen_US
dc.identifier.doi10.1002/path.5349
dc.identifier.pmid31579936


This item appears in the following Collection(s)

Show simple item record