title: [Small molecules--principal participants of pathogenesis of rheumatoid arthritis].
abstract: Poorly known pathogenetic mechanisms of rheumatoid arthritis (RA) including apoptosis and aging are considered with special reference to dysregulation of the p53 protein system. The main p53 regulators, p21 and PUMA proteins, as well as p53 antagonist, Mdm22 are described. The intensity of apoptosis varies throughout RA evolution from low to high at the early and late stages of the pathological process respectively. These variations are responsible for the hyperproliferative status of the synovial membrane. New PUMA-induced p53-independent mechanisms of apoptosis are described. Mdm2 may decrease activity of apoptosis of synovial cells. The role of aging in RA pathogenesis is due to impaired activity of p21 associated with increased invasive potential of synovial cells. It is concluded that induction of apoptosis of synovial membrane cells may be a relevant therapeutic strategy for RA which implies the necessity of further studying the role of small molecules, viz. p53, p21 and PUMA, in its pathogenesis.
authors.forename: A Iu
authors.initials: AIu
authors.lastname: Doroshevskaia
authors.forename: P M
authors.initials: PM
authors.lastname: Kondratovskiĭ
authors.forename: A I
authors.initials: AI
authors.lastname: Dubikov
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D054462:p21-Activated Kinases