The role of metallothionein II in neuronal differentiation and survival

Metallothionein I and II (MT-I+II) are antioxidant and tissue protective factors. We have previously shown that MT-I+II prevent oxidative stress and apoptotic cell death and are of therapeutic value in brain inflammation. However, MT-I+II are expressed in glia and it remains to be elucidated if MT-I+II can affect neurons directly. It is likely that MT isoforms could be beneficial also during neurodegenerative disorders. In this study, we have examined if MT-II affects survival and neurite extension of dopaminergic and hippocampal neurons. We show for the first time that MT-II treatment can significantly stimulate neurite extension from both dopaminergic and hippocampal neurons. Moreover, MT-II treatment significantly increases survival of dopaminergic neurons exposed to 6-whydroxydopamine (6-OHDA) and protects significantly hippocampal neurons from amyloid P-peptide-induced neurotoxicity. Accordingly, treatment with MT-II may be of therapeutic value in neurodegenerative disorders. (C) 2003 Elsevier B.V. All rights reserved.