title: Aβ-Degrading Proteases: Therapeutic Potential in Alzheimer Disease.
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.
authors.affiliation: Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Office: 5212 Natural Sciences II, Irvine, CA, 92697-1450, USA. m.leissring@uci.edu.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Leissring
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010447:Peptide Hydrolases