Neurotoxicity Research

, Volume 33, Issue 1, pp 213–221 | Cite as

L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential

  • J. S. Metcalf
  • R. A. Dunlop
  • J. T. Powell
  • S. A. Banack
  • P. A. CoxEmail author


In human neuroblastoma cell cultures, non-human primates and human beings, L-serine is neuroprotective, acting through a variety of biochemical and molecular mechanisms. Although L-serine is generally classified as a non-essential amino acid, it is probably more appropriate to term it as a “conditional non-essential amino acid” since, under certain circumstances, vertebrates cannot synthesize it in sufficient quantities to meet necessary cellular demands. L-serine is biosynthesized in the mammalian central nervous system from 3-phosphoglycerate and serves as a precursor for the synthesis of the amino acids glycine and cysteine. Physiologically, it has a variety of roles, perhaps most importantly as a phosphorylation site in proteins. Mutations in the metabolic enzymes that synthesize L-serine have been implicated in various human diseases. Dosing of animals with L-serine and human clinical trials investigating the therapeutic effects of L-serine support the FDA’s determination that L-serine is generally regarded as safe (GRAS); it also appears to be neuroprotective. We here consider the role of L-serine in neurological disorders and its potential as a therapeutic agent.


L-serine Alzheimer’s Disease Therapy Neuroprotection ALS Neurodegeneration 



3-phosphoglycerate dehydrogenase

asc-1, asc-2

Alanine-serine-cysteine transporters 1 or 2


Alzheimer’s disease


Amyotrophic lateral sclerosis


Amyotrophic lateral sclerosis/parkinsonism dementia complex


Activating transcription factor 4


Activating transcription factor 6


Autophagy-related gene 8


Blood brain barrier




Central nervous system


Cerebral spinal fluid


Dorsal root ganglion


Eukaryotic initiation factor 2alpha


Endoplasmic reticulum


Endoplasmic-reticulum-associated protein degradation


Frontotemporal lobar degeneration with motor neuron disease


Frontotemporal lobar degeneration with ubiquitinated inclusions


Frontotemporal dementia with parkinsonism


Glutamate receptors


Guanosine diphosphate


General control nondepressible 2


Generally regarded as safe


Guanosine triphosphate


Hepatic heme-regulated inhibitor


Initiator methionyl tRNA


Inositol-requiring enzyme 1


Messenger ribonucleic acid


Transfer ribonucleic acid


Neurofibrillary tangles


Nuclear factor E2-related factor 2


Protein kinase RNA-like endoplasmic reticulum kinase


Protein kinase R


Phosphoserine aminotransferase


Phosphoserine phosphatase


Proteasome subunit regulatory particle 1


TAR DNA binding protein of 43 kDa


Ubiquitin-positive inclusions


Unfolded protein response


X-box binding protein-1


Spliced X-box binding protein-1


Compliance with Ethical Standards

Competing Interests

The Institute for Ethnomedicine has applied for patents for the use of L-serine to treat neurodegenerative illness (US 13/683,821).


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • J. S. Metcalf
    • 1
  • R. A. Dunlop
    • 1
  • J. T. Powell
    • 1
  • S. A. Banack
    • 1
  • P. A. Cox
    • 1
    Email author
  1. 1.Brain Chemistry LabsThe Institute for EthnomedicineJacksonUSA

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