Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

• Published in: Neuromolecular medicine Vol. 13; no. 4; pp. 223 - 250
• Main Authors: Cai, Zhiyou, Zhao, Bin, Ratka, Anna
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01-12-2011
• Subjects: Advanced glycosylation end products; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid precursor protein; Amyloid Precursor Protein Secretases - metabolism; Animals; Apoptosis; beta -Amyloid; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Blood-Brain Barrier - metabolism; Brain; Brain - metabolism; Cytokines - metabolism; Humans; Inflammation - metabolism; Internal Medicine; Lipoproteins; Matrix Metalloproteinases - metabolism; Membrane permeability; Mice; Neurodegenerative diseases; Neuroglia - metabolism; Neurology; Neurosciences; Oxidative Stress; Permeability; Proteolytic enzymes; Rats; Review Paper; Secretase; Tight junctions; Alzheimer’s disease; Oxidative stress; Amyloid protein
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-011-8155-9

Oxidative stress has been proposed to be an important factor in the pathogenesis of Alzheimer’s disease (AD) and contributed to
β
-amyloid (A
β
) generation. Interaction between oxidative stress and neuro-inflammation leads to Aβ generation. AD is associated with an increase in blood–brain barrier (BBB) permeability due to tight junction involvement. Oxidative stress decreases the expression of low-density lipoprotein receptor-related protein 1 and up-regulates receptor for advanced glycation end products in BBB and increases the BBB permeability, which could potentially lead to increased deposition of A
β
within AD brain. Apoptosis takes place in the pathogenesis of AD, and oxidative stress contributes to apoptosis through both extrinsic pathway and intrinsic pathway. Oxidative stress-induced apoptosis may be a potential factor to A
β
generation. A
β
generation requires two sequential cleavages of APP, with the two proteolytic enzymes:
β
-secretase and
γ
-secretase. Oxidative damage up-regulates A
β
via inducing activity of
β
- and
γ
-secretases. In this review, we will focus on the mechanism and pathway that oxidative stress contributes to A
β
generation.