Modulation of the receptor for advanced glycation end products pathway by natural polyphenols: A therapeutic approach to neurodegenerative diseases

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by the progressive loss of neuronal structure and function, leading to severe cognitive and motor deficits. The intricate and multifactorial nature of these diseases poses significant challenges for effective treatment development. The receptor for advanced glycation end products (RAGE), a transmembrane glycoprotein of the immunoglobulin superfamily, is highly expressed in neurons and glial cells. RAGE plays a crucial role in mediating adverse reactions such as neuroinflammation, oxidative stress, and apoptosis, making it a key target in neurodegeneration. Natural polyphenols are a diverse array of bioactive compounds found in fruits, vegetables, tea, and medicinal herbs, attracting attention for their powerful antioxidant, anti-inflammatory, and neuroprotective properties. Recent evidence suggests that these compounds can modulate the RAGE signaling pathway, thereby inhibiting harmful downstream effects and alleviating neuronal damage. This review systematically examines the latest research on how natural polyphenols interact with and modulate the RAGE pathway. We explore the molecular mechanisms underlying their neuroprotective effects, discuss results from in vitro and in vivo studies, and consider the potential for clinical applications. By synthesizing existing knowledge, we aim to provide valuable insights and a theoretical foundation for developing novel polyphenol-based therapeutic strategies targeting neurodegenerative diseases.