Metallothioneins I and II: neuroprotective significance during CNS pathology.
Metallothioneins (MTs) constitutes a superfamily of highly conserved, low molecular weight polypeptides, which are characterized by high contents of cysteine (sulphur) and metals. As intracellular metal-binding proteins they play a significant role in the regulation of essential metals. The major isoforms of the protein (MT-I and MT-II) are induced by numerous stimuli and pathogens but most importantly their induction by metals is closely linked to the physiological metabolism of zinc and protection from the toxic affects following heavy metal exposure. Although the preservation of their genetic expression across animal phyla suggests that MTs may play an important physiological role, MT-I, II knock out (KO) mice survive to adulthood. In both central and peripheral nervous tissues, MT-I, II have neuroprotective roles, which are also induced by exogenous MT-I and/or MT-II treatment. Hence, MT-I, II may provide neurotherapeutic targets offering protection against neuronal injury and degeneration.
Stankovic
Roger K
RK
Department of Pathology, University of Sydney, NSW, Australia. rogers@med.usyd.edu.au
Chung
Roger S
RS
Penkowa
Milena
M
D000818:Animals; D002490:Central Nervous System / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008668:Metallothionein / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008958:Models, Molecular; D019636:Neurodegenerative Diseases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits
D018696:Neuroprotective Agents; D020033:Protein Isoforms; D012333:RNA, Messenger; D008668:Metallothionein