AGE-RAGE axis culminates into multiple pathogenic processes: a central road to neurodegeneration

Area of Science:

• Biochemistry
• Neuroscience
• Pathology

Background:

• Advanced glycation end-products (AGEs) are toxic compounds formed endogenously and exogenously.
• AGEs modify proteins, affecting their function and interacting with the receptor for AGE (RAGE).
• The AGE-RAGE axis is linked to various diseases, including diabetes, cardiovascular conditions, and aging.

Purpose of the Study:

• To explore the role of the AGE-RAGE axis in neurodegenerative diseases (NGDs).
• To highlight the AGE-RAGE axis as a central instigator of neuropathology.
• To discuss therapeutic interventions targeting the AGE-RAGE axis.

Main Methods:

• Review of existing literature on AGEs, RAGE, and neurodegeneration.
• Analysis of the pathological consequences mediated by the AGE-RAGE axis in the brain.
• Discussion of potential therapeutic targets.

Main Results:

• The AGE-RAGE axis contributes to neurodegeneration through mechanisms like blood-brain barrier disruption and neuroinflammation.
• AGE-RAGE axis dysregulation impacts polyol pathway and antioxidant enzymes.
• This axis is a key factor in the pathogenesis of various NGDs.

Conclusions:

• The AGE-RAGE axis is a critical component in the development of neurodegenerative diseases.
• Inhibitors of Toll-like receptor (TLR) or RAGE TIR domains are promising therapeutic agents for NGDs.
• Clinical perspectives on targeting the AGE-RAGE axis warrant further investigation.