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Neurochemical Research

, Volume 44, Issue 6, pp 1289–1296 | Cite as

Powering Amyloid Beta Degrading Enzymes: A Possible Therapy for Alzheimer’s Disease

  • Nkumbu L. Sikanyika
  • Helena C. Parkington
  • A. Ian Smith
  • Sanjaya KuruppuEmail author
Original Paper

Abstract

The accumulation of amyloid beta (Aβ) in the brain is believed to play a central role in the development and progression of Alzheimer’s disease. Revisions to the amyloid cascade hypothesis now acknowledge the dynamic equilibrium in which Aβ exists and the importance of enzymes involved in the production and breakdown of Aβ in maintaining healthy Aβ levels. However, while a wealth of pharmacological and immunological therapies are being generated to inhibit the Aβ-producing enzymes, β-site APP cleavage enzyme 1 and γ-secretase, the therapeutic potential of stimulating Aβ-degrading enzymes such as neprilysin, endothelin-converting enzyme-1 and insulin-degrading enzyme remains relatively unexplored. Recent evidence indicates that increasing Aβ degradation as opposed to inhibiting synthesis is a more effective strategy to prevent Aβ build-up. Therefore Aβ degrading enzymes have become valuable targets of therapy. In this review, we discuss the pathway of Aβ synthesis and clearance along with the opportunities they present for therapeutic intervention, the benefits of increasing the expression/activity of Aβ-degrading enzymes, and the untapped therapeutic potential of enzyme activation.

Keywords

Alzheimer’s disease Amyloid beta Amyloid beta degrading enzymes Neprilysin Endothelin-converting enzyme 

Notes

Acknowledgements

This work was supported by the Virginia Wilke and John Farrell Postgraduate Research Scholarship, the Yulgilbar Alzheimer’s Research Program and Monash University.

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Authors and Affiliations

  1. 1.Monash Biomedicine Discovery InstituteMonash UniversityClaytonAustralia

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