tailieunhanh - Báo cáo khoa học: Metallothioneins are multipurpose neuroprotectants during brain pathology

Metallothioneins (MTs) constitute a family of cysteine-rich metalloproteins involved in cytoprotection during pathology. In mammals there are four isoforms (MT-I )IV), of which MT-I and -II (MT-I + II) are the best characterized MT proteins in the brain. Accumulating studies have demon-strated MT-I + II as multipurpose factors important for host defense responses, immunoregulation, cell survival and brain repair. | FEBS Journal REVIEW ARTICLE Metallothioneins are multipurpose neuroprotectants during brain pathology Milena Penkowa Section of Neuroprotection Centre of Inflammation and Metabolism at The Faculty of Health Sciences University of Copenhagen Denmark Keywords angiogenesis antioxidants apoptosis defense inflammation metalloproteins neuroregeneration pharmacology Correspondence M. Penkowa Section of Neuroprotection The Faculty of Health Sciences University of Copenhagen Blegdamsvej3 DK-2200 Copenhagen Denmark Fax 45 3 5327217 Tel 45 3 5327222 E-mail Received 15 January 2006 revised 23 February 2006 accepted 28 February 2006 doi Metallothioneins MTs constitute a family of cysteine-rich metalloproteins involved in cytoprotection during pathology. In mammals there are four isoforms MT-I - IV of which MT-I and -II MT-I II are the best characterized MT proteins in the brain. Accumulating studies have demonstrated MT-I II as multipurpose factors important for host defense responses immunoregulation cell survival and brain repair. This review will focus on expression and roles of MT-I II in the disordered brain. Initially studies of genetically modified mice with MT-I II deficiency or endogenous MT-I overexpression demonstrated the importance of MT-I II for coping with brain pathology. In addition exogenous MT-I or MT-II injected intraperitoneally is able to promote similar effects as those of endogenous MT-I II which indicates that MT-I II have both extra- and intracellular actions. In injured brain MT-I II inhibit macrophages T lymphocytes and their formation of interleukins tumor necrosis factor-a matrix metalloproteinases and reactive oxygen species. In addition MT-I II enhance cell cycle progression mitosis and cell survival while neuronal apoptosis is inhibited. The precise mechanisms downstream of MT-I II have not been fully established but convincing data show that MT-I II are essential for coping with .