Amino Acids

, Volume 43, Issue 5, pp 1823–1831 | Cite as

The role of d-amino acids in amyotrophic lateral sclerosis pathogenesis: a review

  • Praveen Paul
  • Jacqueline de Belleroche
Review Article


A potential role for d-amino acids in motor neuron disease/amyotrophic lateral sclerosis (ALS) is emerging. d-Serine, which is an activator/co-agonist at the N-methyl-d-aspartate glutamate receptor subtype, is elevated both in spinal cord from sporadic cases of ALS and in an animal model of ALS. Furthermore, we have shown that a mutation in d-amino acid oxidase (DAO), an enzyme strongly localized to spinal cord motor neurons and brain stem motor nuclei, is associated with familial ALS. DAO plays an important role in regulating levels of d-serine, and its function is impaired by the presence of this mutation and this may contribute to the pathogenic process in ALS. In sporadic ALS cases, elevated d-serine may arise from induction of serine racemase, its synthetic enzyme, caused by cell stress and inflammatory processes thought to contribute to disease progression. Both these abnormalities in d-serine metabolism lead to an increase in synaptic d-serine which may contribute to disease pathogenesis.


Amyotrophic lateral sclerosis (ALS) Motor neuron disease Familial ALS d-Amino acid oxidase (DAO) Serine racemase (SR) 



We are grateful to the Motor neurone Disease Association (UK) and American ALS Association for funding this research.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Neurogenetics Group, Centre for Neuroscience, Division of Brain Sciences, Department of MedicineImperial College LondonLondonUK

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