Physiology, Pathophysiology and Clinical Relevance of D‐Amino Acids Dynamics: From Neurochemistry to Pharmacotherapy

Abstract

Over three decades ago, two independent groups of investigators identified free D‐aspartic and later D‐serine in specific brain nuclei and endocrine glands. This finding revealed a novel, non‐proteinogenic role of these molecules. Moreover, the finding that aged proteins from the human eye crystallin, teeth, bone, blood vessels or the brain incorporate D‐aspartic acids to specific primary protein sequences fostered the hypothesis that aging might be related to D‐amino acid isomerization of body proteins. The experimental confirmation that schizophrenia and neurodegenerative diseases modify plasma free D‐amino acids or tissue levelsnurtured the opportunity of using D‐amino acids as therapeutic agents for several disease treatments, a strategy that prompted the successful current application of D‐amino acids to human medicine.