Memory lapses and occasional incoherent behavior, or intestinal cramps with diarrhea, or protracted cough with low fever, or cardiovascular syndromes, or changes in the pattern of movement of the lower limps, can be signs of an incipient chaperonopathy. Yet many physicians do not know this. Most health care professionals are unfamiliar with chaperonopathies. Clinicians do not look for them because they are unaware of them. Pathologists and clinical biochemists are unprepared to test specimens to detect chaperonopathies. Despite the large amount of information available in the literature, textbooks tend to ignore chaperonopathies. Because of the lack of systematic information in textbooks and courses, chaperonopathies are invisible to practitioners and clinical researchers. This book aims to correct this situation by providing pertinent information in an orderly manner so as to prompt the reader to look for chaperonopathies in patients and seek more information about them. The book serves as an alert signal and as a primer.

Zusammenfassung

This Brief provides a concise review of chaperonopathies, i.e., diseases in which molecular chaperones play an etiologic-pathogenic role. Introductory chapters deal with the chaperoning system and chaperoning teams and networks, HSP-chaperone subpopulations, the locations and functions of chaperones, and chaperone genes in humans. Other chapters present the chaperonopathies in general, including their molecular features and mechanistic classification into by defect, excess, or mistake. Subsequent chapters discuss the chaperonopathies in more detail, focusing on their distinctive characteristics: primary or secondary; quantitative and/or qualitative; structural and hereditary or acquired; genetic polymorphisms; gene dysregulation; age-related; associated with cancer, chronic inflammatory conditions, and autoimmune diseases. The interconnections between the chaperoning and the immune systems in cancer development, chronic inflammation, autoimmunity, and ageing are outlined, which leads to a discussion on the future prospects of chaperonotherapy. The latter may consist of chaperone gene and protein replacement/supplementation in cases of deficiency and of gene or protein blocking when the chaperone actively promotes disease. The last chapter presents the extracellular chaperones and details on how the chaperone Hsp60 is secreted into the extracellular space and, thus, appears in the blood of cancer patients with potential to participate in carcinogenesis and chronic inflammation and autoimmunity. Chaperones as clinically useful biomarkers are mentioned when pertinent. Likewise, guidelines for clinical evaluation of chaperonopathies and for their histopathological and molecular identification are provided throughout. The book also provides extensive bibliography organized by chapter and topic with comments.

Inhalt

Overview and book plan.- Chaperones: General characteristics and classifications.- The chaperonopathies: classification, mechanisms, structural features.- Structural and hereditary chaperonopathies: mutation.- Other genetic chaperonopathies.- Acquired chaperonopathies.- Other types of chaperonopathies.- Impact of chaperonopathies in protein homeostasis and beyond.- Extracellular chaperones.