Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?

摘要: Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in early stages disease, they seem to converge on a few characteristic final pathways stages, characterized by inflammation and neurodegeneration. In this review, we put forward hypothesis that advanced glycation end products (AGEs) their precursors, including methylglyoxal, are both biomarkers causative agents ("gerontotoxins") for disorder. Accumulation AGEs normal feature aging, but accelerated AD, where can detected amyloid plaques neurofibrillary tangles. AGE modification may explain many neuropathological biochemical features AD such as extensive protein cross-linking, inflammation, oxidative stress neuronal cell death. We suggest methylglyoxal one major carbonyl species responsible formation AGEs. propose promising pharmacological approach prevent would lower concentration. This achieved, example, decreasing concentration precursors d-glyceraldehyde-3-phosphate allowing higher flux through pentose phosphate pathway or increasing detoxification glyoxalase system. Alternatively, could scavenged types scavengers.