Neurodegeneration results from abnormalities in cerebral metabolism and energy balance within neurons, astrocytes, microglia, or microvascular endothelial cells of the blood-brain barrier. In
Alzheimer's disease, β-
amyloid is considered the primary contributor to neuropathology and neurodegeneration. It now is believed that certain systemic diseases, such as
diabetes mellitus, can contribute to neurodegeneration through the effects of chronic
hyperglycemia/
insulin resistance resulting in protein glycation, oxidative stress and
inflammation within susceptible brain regions. Here, we present an overview of research focusing on the role of protein glycation, oxidative stress, and
inflammation in the neurodegenerative process. Of special interest in this paper is the effect of
methylglyoxal (MGO), a cytotoxic byproduct of
glucose metabolism, elevated in
neurodegenerative disease, and
diabetes mellitus, on cerebral
protein function and oxidative stress. How MGO interacts with
amino acid residues within β-
amyloid, and small
peptides within the brain, is also discussed in terms of the affect on
protein function.