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Aβ-Degrading Proteases: Therapeutic Potential in Alzheimer Disease

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Abstract

The amyloid β-protein (Aβ) plays an indispensable role in the pathogenesis of Alzheimer disease (AD). Aβ is subject to proteolytic degradation by a diverse array of peptidases and proteinases, known collectively as Aβ-degrading proteases (AβDPs). A growing number of AβDPs have been identified that impact Aβ powerfully and in a surprising variety of ways. As such, AβDPs hold considerable therapeutic potential for the treatment and/or prevention of AD. Here, we critically review the relative merits of therapeutic strategies targeting AβDPs compared with current Aβ-lowering strategies focused on immunotherapies and pharmacological modulation of Aβ-producing enzymes. Several innovative advances have increased considerably the feasibility of delivering AβDPs to the brain or enhancing their activity in a non-invasive manner. We argue that therapies targeting AβDPs offer numerous potential advantages that should be explored through continued research into this promising field.

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  1. Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Office: 5212 Natural Sciences II, Irvine, CA, 92697-1450, USA

    Malcolm A. Leissring

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Correspondence to Malcolm A. Leissring.

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Supported by Grant No. 7-11-CD-06 from the American Diabetes Association to M. A. L. No funds were received specifically for the publication of this review.

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The author declares no competing interests.

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Leissring, M.A. Aβ-Degrading Proteases: Therapeutic Potential in Alzheimer Disease. CNS Drugs 30, 667–675 (2016). https://doi.org/10.1007/s40263-016-0364-1

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  • DOI: https://doi.org/10.1007/s40263-016-0364-1

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