Title:D-amino Acids as Novel Blood-based Biomarkers
Volume: 29
Issue: 24
Author(s): Giulia Murtas*Loredano Pollegioni*
Affiliation:
- Department of Biotechnology and Life Sciences, University of Insubria, Varese, 21100, Italy
- Department of Biotechnology and Life Sciences, University of Insubria, Varese, 21100, Italy
Keywords:
D-serine, D-aspartate, early diagnosis, Alzheimer’s disease, schizophrenia, pancreatic cancer, chronic kidney diseases.
Abstract:
Background: D-amino acids are present in the human body originating from
diet, bacterial flora, and endogenous synthesis (at least for D-serine and, probably, D-aspartate).
D-amino acids are involved in important physiological processes (e.g., D-serine
and D-aspartate act on the N-methyl-D-aspartate receptor as co-agonist and agonist, respectively)
and increasing evidence links D-amino acids to different pathological states.
Methods: Determination of D-amino acids levels in blood is mainly based on enantiomeric
separations by high performance liquid chromatography. Because of the low amount
of D-enantiomers compared to the corresponding L-amino acids and the high background
noise associated with biological matrices, positive and negative controls are absolutely
required to obtain reliable values.
Results: Altered levels of D-serine in blood have been reported in several neurological
and psychiatric disorders: it has been proposed as promising biomarker in schizophrenia,
Alzheimer’s disease, and amyotrophic lateral sclerosis. Indeed, D-serine levels seem an
appropriate predictor of anti-depressant response in major depressive disorder and posttraumatic
stress disorder, as well as a prognostic biomarker of early cognitive decline, especially
when considering D-serine and D-proline levels simultaneously. Furthermore,
D-amino acids seem useful biomarkers for pathologies not related to the central nervous
system, such as pancreatic cancer and chronic kidney diseases.
Conclusion: This is the first review focusing on the determination of blood levels of Damino
acids as diagnostic and prognostic biomarkers. The experimental evidence of involvement
of D-amino acids in various physiological pathways suggest investigating
their levels in additional pathologies too, such as diabetes mellitus. In conclusion, the levels
of D-amino acids in blood may represent novel diagnostic peripheral biomarkers for
various disorders. Further studies are required to standardize/automatize the determinations
and for confirming their clinical effectiveness.
