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

Abstract

Recent studies have shown that D-amino acids (DAA) are widelyrepresented in tissues of higher organisms, including man.Specific functions of particular DAA in a healthy body are determined:for instance, D-serine plays an important role in neuroplasticity,memory and learning, while D-aspartate is involved inthe development processes and endocrine functions.Pathogenicity of DAA is associated with over-activation ofNMDA glutamate receptors, conformational changes of normalprotein molecules upon incorporation in the polypeptide chain,and increase inconcentration of reactive oxygen species duringoxidase metabolism of DAA. Assessment of the levels of DAA inbiological fluids, as well as detection of enzyme activity andmutations of the respective genes may serve as diagnostic markersina number of the diseases of the central nervous system(Alzheimers disease, Parkinsons disease, amyotrophic lateralsclerosis, etc). Practical interest to the content and the functionsof DAA is also related to perspectives of elaborating novel therapeuticstrategies aimed at correcting the synthesis/degradationof DAA and modulation of activity of the their receptors.

Keywords

• d-amino acids
• nmdareceptors
• neurodegenerative diseases
• aging