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Int. J. Mol. Sci. 2017, 18(6), 1117; doi:10.3390/ijms18061117

Mammalian Metallothionein-3: New Functional and Structural Insights

1
Department of Chemistry B, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
2
Department of Chemistry and Biochemistry, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080-3021, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Nick Hadjiliadis
Received: 15 April 2017 / Revised: 12 May 2017 / Accepted: 15 May 2017 / Published: 24 May 2017
(This article belongs to the Special Issue Metallothioneins in Bioinorganic Chemistry: Recent Developments)
View Full-Text   |   Download PDF [869 KB, uploaded 24 May 2017]   |  

Abstract

Metallothionein-3 (MT-3), a member of the mammalian metallothionein (MT) family, is mainly expressed in the central nervous system (CNS). MT-3 possesses a unique neuronal growth inhibitory activity, and the levels of this intra- and extracellularly occurring metalloprotein are markedly diminished in the brain of patients affected by a number of metal-linked neurodegenerative disorders, including Alzheimer’s disease (AD). In these pathologies, the redox cycling of copper, accompanied by the production of reactive oxygen species (ROS), plays a key role in the neuronal toxicity. Although MT-3 shares the metal-thiolate clusters with the well-characterized MT-1 and MT-2, it shows distinct biological, structural and chemical properties. Owing to its anti-oxidant properties and modulator function not only for Zn, but also for Cu in the extra- and intracellular space, MT-3, but not MT-1/MT-2, protects neuronal cells from the toxicity of various Cu(II)-bound amyloids. In recent years, the roles of zinc dynamics and MT-3 function in neurodegeneration are slowly emerging. This short review focuses on the recent developments regarding the chemistry and biology of MT-3. View Full-Text
Keywords: metallothionein-3; copper; zinc; metal-thiolate clusters; neurodegeneration; reactive oxygen species; metal homeostasis; amyloid metallothionein-3; copper; zinc; metal-thiolate clusters; neurodegeneration; reactive oxygen species; metal homeostasis; amyloid
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Vašák, M.; Meloni, G. Mammalian Metallothionein-3: New Functional and Structural Insights. Int. J. Mol. Sci. 2017, 18, 1117.

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