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Abstract
Since its initial discovery, current understanding on the functional role of the Receptor
for Advanced Glycation End-products (RAGE) in physiology and in pathology has impressively
grown, especially in consideration of its large ligand repertoire (AGEs, HMGB-1, β
amyloid, S100B/S100A12) and its potential involvement in the pathophysiology of several
chronic human disorders. Downstream RAGE engagement by its ligands, NF-κB signaling
activation has been demonstrated in several cell phenotypes, including neurons and
glia. Based on the observation that in Alzheimer's Disease (AD) brain expression of
RAGE and its ligands is upregulated and that RAGE/NF-κB axis activation can trigger
an autoregulatory loop which further amplifies neuroinflammation and neurodegeneration,
this signaling pathway has been hypothesized to greatly contribute to AD pathophysiology.
Herein we review the vast array of information supporting a detrimental role of RAGE/NF-κB
axis activation in AD brain and discuss those data in the context of recent findings
obtained in our laboratory pointing to an unexpected effect elicited by this signaling
pathway which may rather contribute to reparative mechanisms in AD, namely positive
modulation of adult neurogenesis. Interestingly, the proneurogenic effect resulting
from RAGE/NF-κB axis activation could be induced by molecules which are commonly considered
as mediators of toxicity, like Aβ oligomers and HMGB-1.
Title:
CNS & Neurological Disorders - Drug Targets
Abbreviated Title:
CNSNDDT
Publisher:
Bentham Science Publishers Ltd.
ISSN
(Print):
18715273
Publication date Created:
March
13 2018
Publication date
(Print):
March
13 2018
Volume: 16
Issue: 10
Pages: 1066-1079
Affiliations
[1
]Laboratory of Neuroplasticity, Department of Pharmaceutical Sciences, University of
Piemonte Orientale "Amedeo Avogadro", Via Bovio 6, 28100 Novara, Italy