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. Cox
REVIEW

Abstract

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.

Keywords

L-serine Alzheimer’s Disease Therapy Neuroprotection ALS Neurodegeneration 

Abbreviations

3-PGDH

3-phosphoglycerate dehydrogenase

asc-1, asc-2

Alanine-serine-cysteine transporters 1 or 2

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

ALS/PDC

Amyotrophic lateral sclerosis/parkinsonism dementia complex

ATF4

Activating transcription factor 4

ATF6

Activating transcription factor 6

ATG8

Autophagy-related gene 8

BBB

Blood brain barrier

L-BMAA

β-N-methylamino-L-alanine

CNS

Central nervous system

CSF

Cerebral spinal fluid

DRG

Dorsal root ganglion

eIF2α

Eukaryotic initiation factor 2alpha

ER

Endoplasmic reticulum

ERAD

Endoplasmic-reticulum-associated protein degradation

FTLD-MND

Frontotemporal lobar degeneration with motor neuron disease

FTLD-U

Frontotemporal lobar degeneration with ubiquitinated inclusions

FTDP

Frontotemporal dementia with parkinsonism

GluR

Glutamate receptors

GDP

Guanosine diphosphate

GCN2

General control nondepressible 2

GRAS

Generally regarded as safe

GTP

Guanosine triphosphate

HRI

Hepatic heme-regulated inhibitor

Met-tRNAi

Initiator methionyl tRNA

IRE1

Inositol-requiring enzyme 1

mRNA

Messenger ribonucleic acid

tRNA

Transfer ribonucleic acid

NFTs

Neurofibrillary tangles

NRF-2

Nuclear factor E2-related factor 2

PERK

Protein kinase RNA-like endoplasmic reticulum kinase

PKR

Protein kinase R

PSAT

Phosphoserine aminotransferase

PSP

Phosphoserine phosphatase

Rpt

Proteasome subunit regulatory particle 1

TDP-43

TAR DNA binding protein of 43 kDa

UPIs

Ubiquitin-positive inclusions

UPR

Unfolded protein response

XBP1

X-box binding protein-1

XBP1s

Spliced X-box binding protein-1

Notes

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
  1. 1.Brain Chemistry LabsThe Institute for EthnomedicineJacksonUSA

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