Title:Receptors for Advanced Glycation End Products (RAGE): Promising
Targets Aiming at the Treatment of Neurodegenerative Conditions
Volume: 21
Issue: 2
Author(s): Suélyn Koerich, Gabriela Machado Parreira, Douglas Lamounier de Almeida, Rafael Pinto Vieira*Antônio Carlos Pinheiro de Oliveira*
Affiliation:
- Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901,
Brazil
- Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Brazil
Keywords:
AGEs, neuroinflammation, neurodegeneration, drug development, RAGE, Alzheimer's disease, Parkinson's disease, oxidative stress.
Abstract: Advanced glycation end products (AGEs) are compounds formed after the non-enzymatic
addition of reducing sugars to lipids, proteins, and nucleic acids. They are associated with the development
of various clinical complications observed in diabetes and cardiovascular diseases, such as retinopathy,
nephropathy, diabetic neuropathy, and others. In addition, compelling evidence indicates
that these molecules participate in the progression of neurodegenerative diseases, such as Alzheimer’s
disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Multiple cellular and molecular alterations
triggered by AGEs that could alter homeostasis have been identified. One of the main targets for
AGE signaling is the receptor for advanced glycation end-products (RAGE). Importantly, this receptor
is the target of not only AGEs, but also amyloid β peptides, HMGB1 (high-mobility group box-1),
members of the S100 protein family, and glycosaminoglycans. The activation of this receptor induces
intracellular signaling cascades that are involved in pathological processes and cell death. Therefore,
RAGE represents a key target for pharmacological interventions in neurodegenerative diseases. This
review will discuss the various effects of AGEs and RAGE activation in the pathophysiology of neurodegenerative
diseases, as well as the currently available pharmacological tools and promising drug
candidates.