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.

Highlights

  • Aging, a major risk factor for neurodegenerative disorders, is accompanied with structural, chemical, functional, neuropsychological, and genetic changes, with increased susceptibility to diseases and cognitive impairments [1]

  • This review focuses on the recent advances in our knowledge regarding the structural/chemical and functional properties of MT-3 in metal related biological processes

  • MT-3 is involved in homeostasis of essential transition metals zinc and copper in the brain

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Summary

Introduction

A major risk factor for neurodegenerative disorders, is accompanied with structural, chemical, functional, neuropsychological, and genetic changes, with increased susceptibility to diseases and cognitive impairments [1]. The neuronal growth inhibitory activity of MT-3 appears to be the most prominent biological property of this protein In this regard, an extracellular addition of MT-3, but not MT-1/-2 counteract the ability of AD brain extract to stimulate survival and neuritic sprouting of cultured neurons [10,11]. An extracellular addition of MT-3, but not MT-1/-2 counteract the ability of AD brain extract to stimulate survival and neuritic sprouting of cultured neurons [10,11] Both the growth inhibitory activity and the protective effect of solely MT-3 from the toxic effect of amyloid peptide Aβ1–40 [10] have been linked to its possible role in the pathogenesis of AD. This review focuses on the recent advances in our knowledge regarding the structural/chemical and functional properties of MT-3 in metal related biological processes

Structural and Chemical Properties of Metallothionein-3
Metallothionein-3 in Metal-Linked Neurodegenerative Disorders
Concluding Remarks

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