RAGE axis in neuroinflammation, neurodegeneration and its emerging role in the pathogenesis of amyotrophic lateral sclerosis

Abstract

RAGE, the receptor of advanced glycation end-products, is thought to be one of the potential contributors to the neurodegeneration. It has been shown that RAGE activation triggers an increase in proinflammatory molecules, oxidative stressors and cytokines. RAGE involvement has been documented in the pathogenesis of a number of neurodegenerative diseases such amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, Creutzfeld-Jakob' diseases and various neurodegenerative conditions such as diabetic neuropathy, familial amyloid polyneuropathy, Charcot neuroarthropathy and vasculitic neuropathy. Although the detailed mechanisms of RAGE contribution to the neurodegeneration remains unclear, studies indicate that RAGE detrimental actions are exerted via its binding to the pro-inflammatory ligands such as advanced glycation end-products, S100/calgranulin and amphoterin and subsequent activation of downstream regulatory pathways such as NF-κB, STAT and JKN pathways. Here, in this review we attempt to shed light onto molecular events and pathological pathways involved in neuroinflammation, neurodegeneration and its emerging role in the pathogenesis of amyotrophic lateral sclerosis (ALS)--a progressive and fatal neurodegenerative disorder, summarizing current knowledge and the prospect of RAGE in the pathogenesis of this disastrous disease.

Keywords: ALS; Neurodegeneration; Neuroinflammation; Oxidative stress; RAGE.