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Biochemistry Research International
Volume 2011, Article ID 721463, 13 pages
Review Article

Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease

Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK

Received 17 August 2010; Accepted 7 September 2010

Academic Editor: Simon J. Morley

Copyright © 2011 Mallory Gough et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alzheimer's disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (A 𝛽 -)peptides in the brain causing progressive neuronal death. A 𝛽 -peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contrast to this detrimental “amyloidogenic” form of proteolysis, a range of zinc metalloproteinases can process APP via an alternative “nonamyloidogenic” pathway in which the protein is cleaved within its A 𝛽 region thereby precluding the formation of intact A 𝛽 -peptides. In addition, other members of the zinc metalloproteinase family can degrade preformed A 𝛽 -peptides. As such, the zinc metalloproteinases, collectively, are key to downregulating A 𝛽 generation and enhancing its degradation. It is the role of zinc metalloproteinases in this “positive side of proteolysis in Alzheimer's disease” that is discussed in the current paper.