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

Chem Rec. 2024 Oct;24(10):e202400013. doi: 10.1002/tcr.202400013. Epub 2024 Sep 24.

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.

Keywords: D-Ser and schizophrenia treatment; D-amino acids; D-amino acids pharmacotherapy; D-aspartic in aged proteins; gliotransmission.

Publication types

  • Review

MeSH terms

  • Aging / metabolism
  • Amino Acids* / chemistry
  • Amino Acids* / metabolism
  • Animals
  • Brain / metabolism
  • Clinical Relevance
  • D-Aspartic Acid / chemistry
  • D-Aspartic Acid / metabolism
  • Humans
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism
  • Serine / chemistry
  • Serine / metabolism
  • Stereoisomerism

Substances

  • Amino Acids
  • Serine
  • D-Aspartic Acid