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

Alzheimer's disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (A𝛽-)peptides in the brain causing progressive neuronal death. A𝛽-peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contras...

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Main Authors: Mallory Gough, Catherine Parr-Sturgess, Edward Parkin
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Biochemistry Research International
Online Access:http://dx.doi.org/10.1155/2011/721463
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author Mallory Gough
Catherine Parr-Sturgess
Edward Parkin
author_facet Mallory Gough
Catherine Parr-Sturgess
Edward Parkin
author_sort Mallory Gough
collection DOAJ
description Alzheimer's disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (A𝛽-)peptides in the brain causing progressive neuronal death. A𝛽-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 A𝛽 region thereby precluding the formation of intact A𝛽-peptides. In addition, other members of the zinc metalloproteinase family can degrade preformed A𝛽-peptides. As such, the zinc metalloproteinases, collectively, are key to downregulating A𝛽 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.
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institution Kabale University
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spelling doaj-art-4815c007e5104391aab3397f5fd2365d2025-02-03T01:09:25ZengWileyBiochemistry Research International2090-22472090-22552011-01-01201110.1155/2011/721463721463Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's DiseaseMallory Gough0Catherine Parr-Sturgess1Edward Parkin2Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UKDivision of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UKDivision of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UKAlzheimer's disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (A𝛽-)peptides in the brain causing progressive neuronal death. A𝛽-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 A𝛽 region thereby precluding the formation of intact A𝛽-peptides. In addition, other members of the zinc metalloproteinase family can degrade preformed A𝛽-peptides. As such, the zinc metalloproteinases, collectively, are key to downregulating A𝛽 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.http://dx.doi.org/10.1155/2011/721463
spellingShingle Mallory Gough
Catherine Parr-Sturgess
Edward Parkin
Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease
Biochemistry Research International
title Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease
title_full Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease
title_fullStr Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease
title_full_unstemmed Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease
title_short Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease
title_sort zinc metalloproteinases and amyloid beta peptide metabolism the positive side of proteolysis in alzheimer s disease
url http://dx.doi.org/10.1155/2011/721463
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AT edwardparkin zincmetalloproteinasesandamyloidbetapeptidemetabolismthepositivesideofproteolysisinalzheimersdisease