The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease

MacLeod, R., Hillert, E.-K., Cameron, R. T. and Baillie, G. S. (2015) The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease. Future Science OA, 1(3), FSO11. (doi: 10.4155/fso.15.9) (PMID:28031886) (PMCID:PMC5137966)

Abstract

Alzheimer's disease (AD) is the most common form of dementia in the elderly and its prevalence is set to increase rapidly in coming decades. However, there are as yet no available drugs that can halt or even stabilize disease progression. One of the main pathological features of AD is the presence in the brain of senile plaques mainly composed of aggregated β amyloid (Aβ), a derivative of the longer amyloid precursor protein (APP). The amyloid hypothesis proposes that the accumulation of Aβ within neural tissue is the initial event that triggers the disease. Here we review research efforts that have attempted to inhibit the generation of the Aβ peptide through modulation of the activity of the proteolytic secretases that act on APP and discuss whether this is a viable therapeutic strategy for treating AD.<p></p> Alzheimer's disease (AD) is the most common form of dementia in the elderly but as yet there are no drugs that can halt the progression of this disease. In a theory called the ‘amyloid hypothesis’, researchers have proposed that the accumulation of a small protein fragment called beta amyloid or Aβ within brain tissue is the event which triggers Alzheimer's disease. Aβ is a derivative of the longer amyloid precursor protein (APP). Here we review research efforts that have attempted to inhibit the generation of Aβ through modulation of proteins called secretases which cut APP into Aβ. Author edits made on: 20 May 2015.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Baillie, Professor George and Cameron, Mr Ryan and MacLeod, Miss Ruth
• Authors: MacLeod, R., Hillert, E.-K., Cameron, R. T., and Baillie, G. S.
• Subjects: ?? Alzheimer's disease ??; ?? alpha ??; ?? amyloid hypothesis ??; ?? beta ??; ?? beta amyloid ??; ?? gamma ??; ?? secretase ??
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Future Science OA
• Publisher: Future Science
• ISSN: 2056-5623
• ISSN (Online): 2056-5623
• Copyright Holders: Copyright © 2015 R MacLeod et al.
• First Published: First published in Future Science OA 1(3):
• Publisher Policy: Reproduced under a Creative Commons License