D-Amino Acids in Normal Ageing and Pathogenesis
of Neurodegenerative Diseases

A. V. Chervyakov^a,1, N. V. Gulyaeva^b, and M. N. Zakharova^a

^aResearch Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia

^bInstitute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia

Received August 9, 2010

Abstract—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 endo-
crine 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 toxic-
ity, 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 muta-
tions 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 therapeu-
tic possibilities because they have specific and highly effective actions.

Keywords: D-AAs, racemases, D-AA oxidase, NMDA receptors, neurodegenerative diseases, ageing

DOI: 10.1134/S1819712411020036

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