Is it all the RAGE? Defining the role of the receptor for advanced glycation end products in Parkinson's disease

The receptor for advanced glycation end products (RAGE) is a multiligand protein that has been reported to be a critical modulator of neuroinflammation in Alzheimer's disease (AD), but it is also involved in nerve repair, transcytosis of proteins through the blood –brain barrier (including amyloid β peptide), modulation of neuronal apoptosis, and even in neuronal differentiation. A recent study showed that α-synuclein fibrils bind to RAGE, and we review the possible roles of this receptor in Parkinson's disease (PD). AbstractThe receptor for advanced glycation end products (RAGE) is a transmembrane receptor that belongs to the immunoglobulin superfamily and is extensively associated with chronic inflammation in non-transmissible diseases. As chronic inflammation is consistently present in neurodegenerative diseases, it was largely assumed that RAGE could act as a critical modulator of neuroinflammation in Parkinson's disease (PD), similar to what was reported for Alzheimer's disease (AD), where RAGE is postulated to mediate pro-inflammatory signaling in microglia by binding to amyloid- β peptide. However, accumulating evidence from studies of RAGE in PD models suggests a less obvious scenario. Here, we review physiological aspects of RAGE and address the current questions about the potential involvement of this receptor in the cellular events that may be critical for the developm ent and progression of PD, exploring possible mechanisms beyond the classical view of the mi...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research