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Role and Regulation of Copper and Zinc Transport Proteins in the Central Nervous System

Abstract:

The trace elements copper and zinc are essential for the molecular and physiological functions of the central nervous system (CNS). These cations act as cofactors for enzymes that regulate every aspect of CNS function, including neuronal development and plasticity, neurotransmitter synthesis and processing, cellular metabolism and energy production, and gene expression. Imbalances in zinc have been associated with a variety of clinical disorders, including Alzheimer's disease (AD) and Parkinson's disease. Zinc has also been implicated in the neuronal damage and death associated with ischemia, seizure disorders, and brain trauma. Genetic disorders characterized by copper toxicity and copper deficiency have severe neurological consequences. Thus, it is important that subcellular copper and zinc balance be maintained precisely. This task is accomplished by several families of metal-specific transport proteins. For each metal, this chapter will begin with a brief introduction to the role of this metal in the CNS. This will be followed by the function and regulation of the known transport proteins involved in cellular uptake, intracellular trafficking, and cellular export in the CNS. There will also be discussions of the clinical implications of zinc and copper transporter abnormalities as well as the possible ways that an understanding of these transporters could lead to the development of new treatments for a variety of neurological disorders.

Keywords

  • Zinc Deficiency
  • Zinc Transporter
  • Central Nervous System Function
  • Free Zinc
  • Cellular Zinc

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Abbreviations

AD:

Alzheimer's disease

AE:

acrodermatitis enteropathica

AMPA:

alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid glutamate receptor

ATP7A:

Menkes protein, MNK

ATP7B:

Wilsons protein, WND

BSE:

bovine spongiform encephalopathy

CCK:

cholecystokinin

CCO:

cytochrome c oxidase

CCS:

copper chaperone for SOD

CJD:

Creutzfeldt‐Jakob disease

CNS:

central nervous system

Cp:

ceruloplasmin

Cu:

copper

DβM:

dopamine beta monooxygenase

DMT1:

divalent metal transporter‐1

FKBP52:

FK506‐binding protein 52

GABA:

gamma‐aminobutyric acid

GABAA :

GABAA receptor

Glu:

glutamate

GnRH:

gonadotropin‐releasing hormone

GPI:

glycosylphosphatidylinositol

LZT:

LIV‐1 subfamily of ZIP zinc transporters

MMP:

matrix metalloproteinase protein

MNK:

Menkes protein, ATP7A

MSH:

melanocortin stimulating hormone

MT:

metallothionein

NMDA:

N‐methyl‐d‐aspartate glutamate receptor

NPY:

neuropeptide Y

NRF:

nuclear respiratory factor

PAM:

peptidylglycine α‐amidating monooxygenase

SOD:

superoxide dismutase

TGN:

trans‐Golgi network

TRH:

thyrotropin‐releasing hormone

VGCaC:

Voltage‐gated calcium channels

VIP:

vasoactive intestinal polypeptide

WND:

Wilsons disease protein, APT7B

ZIP:

Zrt/Irt‐like proteins

Zn:

zinc

ZnT:

zinc transporter

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Levenson, C.W., Tassabehji, N.M. (2007). Role and Regulation of Copper and Zinc Transport Proteins in the Central Nervous System. In: Lajtha, A., Reith, M.E.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30380-2_13

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