d-serine in physiological and pathological brain aging

Biochim Biophys Acta Proteins Proteom. 2021 Jan;1869(1):140542. doi: 10.1016/j.bbapap.2020.140542. Epub 2020 Sep 18.


Among aging-induced impairments, those affecting cognitive functions certainly represent one the most major challenge to face to improve elderly quality of life. In last decades, our knowledge on changes in the morphology and function of neuronal networks associated with normal and pathological brain aging has rapidly progressed, initiating the development of different pharmacological and behavioural strategies to alleviate cognitive aging. In particular, experimental evidences have accumulated indicating that the communication between neurons and its plasticity gradually weakens with aging. Because of its pivotal role for brain functional plasticity, the N-Methyl‑d-Aspartate receptor subtype of glutamate receptors (NMDAr) has gathered much of the experimental interest. NMDAr activation is regulated by many mechanisms. Among is the mandatory binding of a co-agonist, such as the amino acid d-serine, in order to activate NMDAr. This mini-review presents the most recent information indicating how d-serine could contribute to mechanisms of physiological cognitive aging and also considers the divergent views relative of the role of the NMDAr co-agonist in Alzheimer's disease.

Keywords: Alzheimer's disease; Glutamate; NMDA receptors; Serine racemase; Synaptic plasticity; l-serine.

Publication types

  • Review

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Cognition / physiology
  • Gene Expression
  • Glucose / metabolism
  • Glutamic Acid / metabolism
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Memory / physiology
  • Neuronal Plasticity / physiology*
  • Neurons / metabolism
  • Neurons / pathology
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / metabolism
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Serine / metabolism*


  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Serine
  • Racemases and Epimerases
  • serine racemase
  • Glucose