Neprilysin and Amyloid Beta Peptide Degradation

Authors: Hersh, Louis B.; Rodgers, David W.

Source: Current Alzheimer Research, Volume 5, Number 2, April 2008 , pp. 225-231(7)

Publisher: Bentham Science Publishers

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Abstract:

Neprilysin is a zinc metalloendopeptidase with relatively broad substrate specificity. The enzyme is localized to the plasma membrane of cells where it can function to degrade extracellular peptides. Structural studies show that neprilysin preferentially cleaves peptides on the amino side of hydrophobic amino acids. Neprilysin has been implicated in the catabolism of amyloid β peptides in the brain and as such has received considerable attention, particularly as a therapeutic target for Alzheimer's disease. An inverse relationship between neprilysin levels and amyloid β peptide levels and between neprilysin levels and amyloid plaque formation has been observed in human brain. Neprilysin levels decline with aging in the temporal and frontal cortex possibly contributing to higher amyloid β peptide levels. A number of studies have shown that increasing neprilysin levels in the brain leads to a decrease in brain amyloid β peptide levels. Most recently a potential relationship between amyloid β peptide synthesis from the amyloid precursor protein and neprilysin activity has been proposed.

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156720508783954703

Publication date: 2008-04-01

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Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

Neprilysin and Amyloid Beta Peptide Degradation

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