D-amino acids in normal ageing and pathogenesis of neurodegenerative diseases

We review the potential role of D-amino acids (D-AAs) in the functioning of the human CNS. About 50 years ago, scientists believed that D-AAs do not exist in living organisms. Studies in the last decades have shown that D-AAs are widely present in the tissues of higher organisms, including humans. D-serine plays an important role in neuroplasticity, memory, and learning; D-aspartate is involved in developmental and endocrine functions. The main pathways for the appearance and metabolism of D-AAs have been described. The pathogenicity of D-AAs is associated with excess activation of NMDA receptors and incorporation into normal protein molecules (conformational changes), which results in functional inactivation of the protein or its toxicity, and an increase in the concentration of reactive oxygen species (oxidative stress) during disintegration of D-AAs by D-AA oxidase (DAAO). The level of D-AAs in biological fluids, the activity of enzymes, and mutations in genes that encode these enzymes may be used as a diagnostic marker in some diseases. We believe that it is possible to develop methods that will alter the intake of D-AAs, their synthesis, and degradation and to use D-AAs as modulators of receptors, which may be useful for the development of new therapeutic strategies. Finally, the use of exogenous D-AAs (unbound or as a component of proteins) may also provide new therapeutic possibilities because they have specific and highly effective actions.