Chaperonopathies and chaperonotherapy

Abstract 

The study of molecular chaperones (genetics, structure, location, physiology, pathology, and therapeutics) has developed into a science with specific objectives, methods, and hypotheses, a discipline we called chaperonology. Subdisciplines of chaperonology include the study of pathological chaperones (chaperonopathies) and the analysis of their genes in sequenced genomes (chaperonomics). Chaperonopathies are pathological conditions in which one type of chaperone is deficient due to a genetic or acquired defect that modifies the chaperone’s structure and/or makes the chaperone unavailable for functioning when needed. Experimental and clinical data show that chaperones and their genes can be used for treating various pathological conditions, thus justifying the development of chaperonotherapy. We discuss recent work showing that chaperonotherapy is on solid foundations: the data demonstrate that molecular chaperones counteract pathogenetic mechanisms in disease and during stress.

Keywords: Chaperonology, Chaperonopathies, Chaperonotherapy, Stress, Protein misfolding, Protein aggregation

Abbreviations: Hsp, heat-shock protein, TUNEL assay, deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, SOD1, superoxide dismutase 1, FALS, familial amyotrophic lateral sclerosis, SDS, sodium-dodecylsulfate, BAG1, Bcl-2-associated athanogene 1, where Bcl stands for B-cell leukemia/lymphoma 2, APP, amyloid precursor protein, ER, endoplasmic reticulum, PPIase, peptidyl-prolyl cis–trans isomerase, AS, α-Synuclein, UPS, ubiquitin–proteasome system, DRM, desmin-related myopathy, SBMA, spinal and bulbar muscular atrophy, AR, androgen receptor, GGA, geranylgeranylacetone, siRNA, small inhibitory RNA