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13 - Copper and zinc in Alzheimer's disease and amyotrophic lateral sclerosis

from Part I - Basic aspects of neurodegeneration

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal ,
Anthony E. Lang  and
Albert C. Ludolph
By
Avi L. Friedlich  and
Ashley I. Bush
M. Flint Beal
Affiliation:
Cornell University, New York
Anthony E. Lang
Affiliation:
University of Toronto
Albert C. Ludolph
Affiliation:
Universität Ulm, Germany
Avi L. Friedlich
Affiliation:
Laboratory for Oxidation Biology, Genetics and Aging Research Unit, Massachusetts General Hospital, MA, USA
Ashley I. Bush
Affiliation:
Laboratory for Oxidation Biology, Genetics and Aging Research Unit, Massachusetts General Hospital, MA, USA
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Summary

Introduction

The non-infectious neurodegenerative disorders, Alzheimer's disease, and amyotrophic lateral sclerosis are heterogeneous with respect to etiology, neuropathology and clinical presentation. Yet, these disorders share a number of features in common to suggest some common pathogenic events. Each disorder is age related and is characterized by progressive and symmetric degeneration of discrete populations of neurons. Each disorder is associated with biochemical markers of oxidative attack, and each is associated with deposition of a CuZn metalloprotein in affected tissue.

Molecular genetic analysis has linked autosomal dominant forms of AD, PD, and amyotrophic lateral sclerosis, respectively, to mutations in ß-amyloid precursor protein, α-synuclein, and superoxide dismutase 1. Each of these proteins or its proteolytic products may aggregate in affected tissue during the course of disease.

In this chapter we summarize current knowledge of CNS Cu and Zn metabolism in normal physiology. Then, focusing on AD and ALS, we review evidence for pathophysiologic Cu and Zn metabolism and evidence linking Cu and Zn to the physiologic and toxic activities of ß-amyloid protein and superoxide dismutase 1.

Protein interactions in brain copper and zinc metabolism

At the active site of many enzymes, Cu participates in one-electron transfer reactions. Zn, which is electrochemically inert, maintains structural stability of many proteins. In addition to these essential and ubiquitous roles for Cu and Zn, brain-specific functions exist for these metals.

Type
Chapter
Information
Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
 , pp. 157 - 165
Publisher: Cambridge University Press
Print publication year: 2005

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