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

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...

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Bibliographic Details
Published in:Amino acids 2012-11, Vol.43 (5), p.1823-1831
Main Authors: Paul, Praveen, de Belleroche, Jacqueline
Format: Article
Language:English
Subjects:
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - metabolism
Amyotrophic Lateral Sclerosis - physiopathology
Analytical Chemistry
Animals
Biochemical Engineering
Biochemistry
Biomedical and Life Sciences
Brain - metabolism
Brain - physiopathology
D-Amino-Acid Oxidase - genetics
D-Amino-Acid Oxidase - metabolism
Disease Progression
Gene Expression
Humans
Life Sciences
Mice
Neurobiology
Neurotransmitter Agents - metabolism
Proteomics
Racemases and Epimerases - genetics
Racemases and Epimerases - metabolism
Receptors, N-Methyl-D-Aspartate - metabolism
Review Article
Serine - metabolism
Spinal Cord - metabolism
Spinal Cord - physiopathology
Stereoisomerism
Synaptic Transmission
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Summary: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.
ISSN:0939-4451
1438-2199
DOI:10.1007/s00726-012-1385-9