Protein glycoxidation in neuropsychiatric disorders—from basic research to clinical practice

This review integrates current findings on protein glycation, glycoxidation, and carbonyl stress in selected neurodegenerative and neuropsychiatric disorders, with a particular focus on mechanistic pathways relevant to Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, and depression, as well as on their potential clinical relevance, including biomarker development and antiglycation interventions. These processes are increasingly recognised as cross-cutting features in various neuropsychiatric conditions. Despite this mechanistic relevance, no neuropsychiatric drugs have been convincingly demonstrated to exert direct antiglycation activity in vivo . The majority of published findings concern indirect modulation of carbonyl stress, redox imbalance, and advanced glycation end products (AGEs) and their receptor (RAGE) signalling rather than direct inhibition of glycation. AGEs, particularly the lysine-derived adducts Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML), show potential as diagnostic and prognostic biomarkers in neurodegenerative diseases, although further clinical validation is required. Modulation of protein glycation, carbonyl stress, and AGE–RAGE signalling has emerged as a common mechanistic denominator in various therapeutic strategies explored in neuropsychiatric disorders.