Title:Role of Ageing and Oxidative Stress in Regulation of Amyloid-Degrading Enzymes and Development of Neurodegeneration
VOLUME: 10 ISSUE: 1
Author(s):Natalia N. Nalivaeva and Anthony J. Turner
Affiliation:School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Keywords:Ageing, Alzheimer's disease, amyloid clearance, amyloid-degrading enzymes, neprilysin, oxidative stress, proteolysis.
Abstract:The accumulation of cerebral amyloid β-peptide (Aβ) is a key precipitating factor for neuronal
cell death in Alzheimer’s Disease (AD). However, brain Aβ levels are modifiable since there is
a balance between its formation from the Amyloid Precursor Protein (APP) and its removal by clearance
mechanisms, which can be either through proteolysis or by protein binding and subsequent
transport). Among the major enzymes degrading brain Aβ are several zinc-proteases: neprilysin
(NEP), its homologues NEP2 and the Endothelin Converting Enzymes (ECE-1 and -2) and also the
Insulin-Degrading Enzyme (IDE). During the ageing process, and under certain pathological conditions
(e.g. ischemia and stroke), the expression and activity of these enzymes decline, which leads to
a deficit of Aβ clearance and its accumulation in the brain. Some of these changes in the enzyme
properties are due to their reduced expression and/or structural modification by reactive oxygen species.
In this review paper we shall discuss some mechanisms of regulation of Amyloid-Degrading
Enzymes (ADEs) and possible therapeutic approaches which might prevent their decline with age
and after pathology.
