Title:Role and Therapeutic Potential of RAGE Signaling in Neurodegeneration
Volume: 23
Issue: 12
Author(s): Noah Alexander Kinscherf and Mariana Pehar*
Affiliation:
- Department of Medicine, Division of Geriatrics and Gerontology, University of Wisconsin- Madison, Madison, WI, USA
- Geriatric Research Education Clinical Center, Veterans Affairs Medical Center, Madison, WI, USA
Keywords:
Advanced glycation end products receptor, Alzheimer’s disease, amyotrophic lateral sclerosis, astrocytes, microglia, neurons, parkinson’s disease.
Abstract: Activation of the receptor for advanced glycation end products (RAGE) has been shown
to play an active role in the development of multiple neurodegenerative diseases, including Alzheimer’s
disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Although originally identified
as a receptor for advanced glycation end products, RAGE is a pattern recognition receptor
able to bind multiple ligands. The final outcome of RAGE signaling is defined in a context and cell
type specific manner and can exert both neurotoxic and neuroprotective functions. Contributing to
the complexity of the RAGE signaling network, different RAGE isoforms with distinctive signaling
capabilities have been described. Moreover, multiple RAGE ligands bind other receptors and
RAGE antagonism can significantly affect their signaling. Here, we discuss the outcome of celltype
specific RAGE signaling in neurodegenerative pathologies. In addition, we will review the different
approaches that have been developed to target RAGE signaling and their therapeutic potential.
A clear understanding of the outcome of RAGE signaling in a cell type- and disease-specific
manner would contribute to advancing the development of new therapies targeting RAGE. The ability
to counteract RAGE neurotoxic signaling while preserving its neuroprotective effects would be
critical for the success of novel therapies targeting RAGE signaling.
