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

Metcalf, J. S.; Dunlop, R. A.; Powell, J. T.; Banack, S. A.; Cox, P. A.

doi:10.1007/s12640-017-9814-x

REVIEW
Published: 19 September 2017

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

J. S. Metcalf¹^na1,
R. A. Dunlop¹^na1,
J. T. Powell¹,
S. A. Banack¹ &
P. A. Cox¹

Neurotoxicity Research volume 33, pages 213–221 (2018)Cite this article

1487 Accesses
35 Citations
15 Altmetric
Metrics details

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

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

References

Acuna-Hidalgo R, Schanze D, Kariminejad A et al (2014) Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. Am J Hum Genet 95:285–293. https://doi.org/10.1016/j.ajhg.2014.07.012
CAS Article PubMed PubMed Central Google Scholar
Artom C, Fishman WH, Morehead RP (1945) The relative toxicity of l- and dl-serine in rats. Proc Soc Exp Biol Med 60:284–287
CAS Article PubMed Google Scholar
Benevenga NJ, Harper AE (1967) Alleviation of methionine and homocystine toxicity in the rat. J Nutr 93:44–52
CAS PubMed Google Scholar
Canu N, Ciotti MT, Pollegioni L (2014) Serine racemase: a key player in apoptosis and necrosis. Front Synaptic Neurosci 6:1–15. https://doi.org/10.3389/fnsyn.2014.00009
Article Google Scholar
Catsman-Berrevoets C, de Klerk J, Huymans J et al (1997) Inborn error of serine biosynthesis, a new phenotype. Eur J Paediatr Neurol 1:A43. https://doi.org/10.1177/135245859800400610
Google Scholar
Cheng R, Banack SA (2009) Previous studies underestimate BMAA concentrations in cycad flour. Amyotroph Lateral Scler 10(Suppl 2):41–43. https://doi.org/10.3109/17482960903273528
CAS Article PubMed Google Scholar
Cohen P (2002) The origins of protein phosphorylation. Nat Cell Biol 4:E127–E130. https://doi.org/10.1038/ncb0502-e127
CAS Article PubMed Google Scholar
Cox PA, Metcalf JS (2017) Traditional food items in Ogimi, Okinawa: L-serine content and the potential for neuroprotection. Curr Nutr Rep 6(1):24–31. https://doi.org/10.1007/s13668-017-0191-0
CAS Article PubMed PubMed Central Google Scholar
Cox PA, Banack SA, Murch SJ (2003) Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proc Natl Acad Sci U S A 100:13380–13383. https://doi.org/10.1073/pnas.2235808100
CAS Article PubMed PubMed Central Google Scholar
Cox PA, Banack SA, Murch SJ et al (2005) Diverse taxa of cyanobacteria produce beta-N-methylamino-L-alanine, a neurotoxic amino acid. Proc Natl Acad Sci U S A 102:5074–5078. https://doi.org/10.1073/pnas.0501526102
CAS Article PubMed PubMed Central Google Scholar
Cox PA, Davis DA, Mash DC, et al (2016) Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain. Proc R Soc B 283(1823). doi: https://doi.org/10.1098/rspb.2015.2397
de Koning TJ, Klomp LWJ (2004) Serine-deficiency syndromes. Curr Opin Neurol 17:197–204
Article PubMed Google Scholar
de Koning TJ, Duran M, Van Maldergem L et al (2002) Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. J Inherit Metab Dis 25:119–125. https://doi.org/10.1023/A:1015624726822
Article PubMed Google Scholar
de Koning TJ, Snell K, Duran M et al (2003) L-serine in disease and development. Biochem J 371:653–661. https://doi.org/10.1042/BJ20021785
Article PubMed PubMed Central Google Scholar
de Koning T, Klomp L, van Oppen A et al (2004) Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet 364:2221–2222. https://doi.org/10.1016/S0140-6736(04)17596-X
Article PubMed Google Scholar
DeNicola GM, Chen P-H, Mullarky E et al (2015) NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet 47:1475–1481. https://doi.org/10.1038/ng.3421
CAS Article PubMed PubMed Central Google Scholar
Duncan MW (1992) beta-Methylamino-L-alanine (BMAA) and amyotrophic lateral sclerosis-parkinsonism dementia of the western Pacific. Ann N Y Acad Sci 648:161–168
CAS Article PubMed Google Scholar
Dunlop RA, Cox PA, Banack SA, Rodgers KJ (2013) The non-protein amino acid BMAA is misincorporated into human proteins in place of L-serine causing protein misfolding and aggregation. PLoS One 8:e75376. https://doi.org/10.1371/journal.pone.0075376
CAS Article PubMed PubMed Central Google Scholar
Dunlop RA, Main BJ, Rodgers KJ (2014) The deleterious effects of non-protein amino acids from desert plants on human and animal health. J Arid Environ 112:152–158. https://doi.org/10.1016/j.jaridenv.2014.05.005
Article Google Scholar
Dunlop RA, Powell J, Metcalf JS, et al (2017) L-serine-mediated neuroprotection includes the upregulation of the ER stress chaperone protein disulphide isomerase (PDI). Neurotoxicity Research (in press).
El-Hattab AW (2016) Serine biosynthesis and transport defects. Mol Genet Metab 118:153–159. https://doi.org/10.1016/j.ymgme.2016.04.010
CAS Article PubMed Google Scholar
Esterhuizen M, Downing TG (2008) Beta-N-methylamino-L-alanine (BMAA) in novel South African cyanobacterial isolates. Ecotoxicol Environ Saf 71:309–313. https://doi.org/10.1016/j.ecoenv.2008.04.010
CAS Article PubMed Google Scholar
Fuchs SA, Berger R, de Koning TJ (2011) D-serine: the right or wrong isoform? Brain Res 1401:104–117. https://doi.org/10.1016/j.brainres.2011.05.039
CAS Article PubMed Google Scholar
Furuya S, Watanabe M (2003) Novel neuroglial and glioglial relationships mediated by L-serine metabolism. Arch Histol Cytol 66:109–121. https://doi.org/10.1679/aohc.66.109
CAS Article PubMed Google Scholar
Furuya S, Tabata T, Mitoma J et al (2000) L-serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons. Proc Natl Acad Sci U S A 97:11528–11533. https://doi.org/10.1073/pnas.200364497
CAS Article PubMed PubMed Central Google Scholar
Furuya S, Yoshida K, Kawakami Y et al (2008) Inactivation of the 3-phosphoglycerate dehydrogenase gene in mice: changes in gene expression and associated regulatory networks resulting from serine deficiency. Funct Integr Genomics 8:235–249. https://doi.org/10.1007/s10142-007-0072-5
CAS Article PubMed Google Scholar
Garofalo K, Penno A, Schmidt BP et al (2011) Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J Clin Invest 121:4735–4745. https://doi.org/10.1172/JCI57549
CAS Article PubMed PubMed Central Google Scholar
Gibson L, Holmgreen SP, Huang DC et al (1996) bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene 13:665–675
CAS PubMed Google Scholar
Glover WB, Mash DC, Murch SJ (2014) The natural non-protein amino acid N-β-methylamino-L-alanine (BMAA) is incorporated into protein during synthesis. Amino Acids. https://doi.org/10.1007/s00726-014-1812-1
Hardy RW, Tantengco VO, Baumann CA (1960) Effects of amino acids on the excretion of various proteins by the rat. J Nutr 70:438–446
CAS PubMed Google Scholar
Hart CE, Race V, Achouri Y et al (2007) Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. Am J Hum Genet 80:931–937. https://doi.org/10.1086/517888
CAS Article PubMed PubMed Central Google Scholar
Hasegawa M, Arai T, Nonaka T et al (2008) Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol 64:60–70. https://doi.org/10.1002/ana.21425
CAS Article PubMed PubMed Central Google Scholar
Hirabayashi Y, Furuya S (2008) Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival. Prog Lipid Res 47:188–203. https://doi.org/10.1016/j.plipres.2008.01.003
CAS Article PubMed Google Scholar
Hirano A, Zimmerman HM (1962) Alzheimer’s neurofibrillary changes: a topographic study. Arch Neurol 7:227–242
CAS Article PubMed Google Scholar
Hirano A, Kurland LT, Krooth RS, Lessell S (1961) Parkinsonism-dementia complex, an endemic disease on the island of Guam. I. Clinical features. Brain 84:642–661
CAS Article PubMed Google Scholar
Humphrey SJ, James DE, Mann M (2015) Protein phosphorylation: a major switch mechanism for metabolic regulation. Trends Endocrinol Metab 26:676–687. https://doi.org/10.1016/j.tem.2015.09.013
CAS Article PubMed Google Scholar
Hunter T (2012) Why nature chose phosphate to modify proteins. Philos Trans R Soc Lond Ser B Biol Sci 367:2513–2516. https://doi.org/10.1098/rstb.2012.0013
CAS Article Google Scholar
Huttlin EL, Jedrychowski MP, Elias JE et al (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143:1174–1189. https://doi.org/10.1016/j.cell.2010.12.001
CAS Article PubMed PubMed Central Google Scholar
Iqbal K, Liu F, Gong C-X (2016) Tau and neurodegenerative disease: the story so far. Nat Rev Neurol 12:15–27. https://doi.org/10.1038/nrneurol.2015.225
CAS Article PubMed Google Scholar
Jaeken J, Detheux M, Van Maldergem L et al (1996a) 3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis. Arch Dis Child 74:542–545
CAS Article PubMed PubMed Central Google Scholar
Jaeken J, Detheux M, Van Maldergem L et al (1996b) 3-Phosphoglycerate dehydrogenase deficiency and 3-phosphoserine phosphatase deficiency: inborn errors of serine biosynthesis. J Inherit Metab Dis 19:223–226
CAS Article PubMed Google Scholar
Kalhan SC, Hanson RW (2012) Resurgence of serine: an often neglected but indispensable amino acid. J Biol Chem 287:19786–19791. https://doi.org/10.1074/jbc.R112.357194
CAS Article PubMed PubMed Central Google Scholar
Kasai Y, Tachikawa M, Hirose S et al (2011) Transport systems of serine at the brain barriers and in brain parenchymal cells. J Neurochem 118:304–313. https://doi.org/10.1111/j.1471-4159.2011.07313.x
CAS Article PubMed Google Scholar
Kurosawa M, Matsumoto G, Sumikura H et al (2016) Serine 403-phosphorylated p62/SQSTM1 immunoreactivity in inclusions of neurodegenerative diseases. Neurosci Res 103:64–70. https://doi.org/10.1016/j.neures.2015.08.002
CAS Article PubMed Google Scholar
Lee A-H, Iwakoshi NN, Glimcher LH (2003) XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 23:7448–7459
CAS Article PubMed PubMed Central Google Scholar
Levine TD, Miller RG, Bradley WG et al (2017) Phase I clinical trial of safety of L-serine for ALS patients. Amyotroph Lateral Scler Front Degener 18:107–111. https://doi.org/10.1080/21678421.2016.1221971
CAS Article Google Scholar
Lockart RZ, Eagle H (1959) Requirements for growth of single human cells. Science 129:252–254
Article PubMed Google Scholar
Mackenzie IRA, Rademakers R (2008) The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia. Curr Opin Neurol 21:693–700. https://doi.org/10.1097/WCO.0b013e3283168d1d
CAS Article PubMed PubMed Central Google Scholar
Maddocks ODK, Berkers CR, Mason SM et al (2012) Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 493:542–546. https://doi.org/10.1038/nature11743
Article PubMed Google Scholar
Mally J, Baranyi M, Vizi ES (1996) Change in the concentrations of amino acids in CSF and serum of patients with essential tremor. J Neural Transm 103:555–560. https://doi.org/10.1007/BF01273153
CAS Article PubMed Google Scholar
Murch SJ, Cox PA, Banack SA et al (2004a) Occurrence of beta-methylamino-l-alanine (BMAA) in ALS/PDC patients from Guam. Acta Neurol Scand 110:267–269. https://doi.org/10.1111/j.1600-0404.2004.00320.x
CAS Article PubMed Google Scholar
Murch SJ, Cox PA, Banack SA (2004b) A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam. Proc Natl Acad Sci U S A 101:12228–12231. https://doi.org/10.1073/pnas.0404926101
CAS Article PubMed PubMed Central Google Scholar
Nelson PT, Alafuzoff I, Bigio EH et al (2012) Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 5:362–381. https://doi.org/10.1097/NEN.0b013e31825018f7
Nestler E, Greengard P (1999) Protein phosphorylation is of fundamental importance in biological regulation. In: Siegel GJ, Agranoff BW, Albers RW et al (eds) Basic neurochemistry: molecular, cellular, and medical aspects, 6th edn. Lippincott-Raven, Philadelphia
Google Scholar
Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133. https://doi.org/10.1126/science.1134108
CAS Article PubMed Google Scholar
Newman EB, Magasanik B (1963) The relation of serine-glycine metabolism to the formation of single-carbon units. Biochim Biophys Acta 78:437–448. https://doi.org/10.1016/0006-3002(63)90905-3
CAS Article PubMed Google Scholar
Nishikawa T (2011) Analysis of free D-serine in mammals and its biological relevance. J Chromatog B 879:3169–3183. https://doi.org/10.1016/j.jchromb.2011.08.030
CAS Article Google Scholar
Pablo J, Banack SA, Cox PA et al (2009) Cyanobacterial neurotoxin BMAA in ALS and Alzheimer’s disease. Acta Neurol Scand 120:216–225. https://doi.org/10.1111/j.1600-0404.2008.01150.x
CAS Article PubMed Google Scholar
Perluigi M, Barone E, Di Domenico F, Butterfield DA (2016) Aberrant protein phosphorylation in Alzheimer disease brain disturbs pro-survival and cell death pathways. Biochim Biophys Acta Mol Basis Dis 1862:1871–1882. https://doi.org/10.1016/j.bbadis.2016.07.005
CAS Article Google Scholar
Savoca R, Ziegler U, Sonderegger P (1995) Effects of L-serine on neurons in vitro. J Neurosci Methods 61:159–167
CAS Article PubMed Google Scholar
Seibenhener M, Babu J (2004) Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol 24:8055–8068. https://doi.org/10.1128/MCB.24.18.8055
CAS Article PubMed PubMed Central Google Scholar
Sim W, Yin H, Choi H-S et al (2015) L-serine supplementation attenuates alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats. J Nutr 145:260–267. https://doi.org/10.3945/jn.114.199711
Article PubMed Google Scholar
Sonenberg N, Hinnebusch AG (2009) Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136:731–745. https://doi.org/10.1016/j.cell.2009.01.042
Spencer PS, Nunn PB, Hugon J et al (1987) Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science 237:517–522
CAS Article PubMed Google Scholar
Sun L, Song L, Wan Q et al (2015) cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions. Cell Res 25:429–444. https://doi.org/10.1038/cr.2015.33
CAS Article PubMed PubMed Central Google Scholar
Tabatabaie L, Klomp LWJ, Rubio-Gozalbo ME et al (2011) Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiency. J Inherit Metab Dis 34:181–184. https://doi.org/10.1007/s10545-010-9249-5
CAS Article PubMed Google Scholar
Tanji K, Miki Y, Ozaki T et al (2014) Phosphorylation of serine 349 of p62 in Alzheimer’s disease brain. Acta Neuropathol Commun 2:50. https://doi.org/10.1186/2051-5960-2-50
Article PubMed PubMed Central Google Scholar
Toshikuni N, Tsutsumi M, Arisawa T (2014) Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease. World J Gastroenterol 20:8393–8406. https://doi.org/10.3748/wjg.v20.i26.8393
Article PubMed PubMed Central Google Scholar
Trojanowski JQ, Ishihara T, Higuchi M et al (2002) Amyotrophic lateral sclerosis/parkinsonism dementia complex: transgenic mice provide insights into mechanisms underlying a common tauopathy in an ethnic minority on Guam. Exp Neurol 176:1–11. https://doi.org/10.1006/exnr.2002.7940
CAS Article PubMed Google Scholar
van der Crabben SN, Verhoeven-Duif NM, Brilstra EH et al (2013) An update on serine deficiency disorders. J Inherit Metab Dis 36:613–619. https://doi.org/10.1007/s10545-013-9592-4
CAS Article PubMed Google Scholar
van Onselen R, Cook NA, Phelan RR, Downing TG (2015) Bacteria do not incorporate β-N-methylamino-L-alanine into their proteins. Toxicon 102:55–61. https://doi.org/10.1016/j.toxicon.2015.05.014
Article PubMed Google Scholar
Vanhelmont T, Vandebroek T, De Vos A et al (2010) Serine-409 phosphorylation and oxidative damage define aggregation of human protein tau in yeast. FEMS Yeast Res 10:992–1005. https://doi.org/10.1111/j.1567-1364.2010.00662.x
CAS Article PubMed Google Scholar
Verleysdonk S, Hamprecht B (2000) Synthesis and release of L-serine by rat astroglia-rich primary cultures. Glia 30:19–26
CAS Article PubMed Google Scholar
Wek R, Jiang H, Anthony T (2006) Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 34:7–11. https://doi.org/10.1042/BST20060007
CAS Article PubMed Google Scholar
Wolosker H, Blackshaw S, Snyder SH (1999) Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission. Proc Natl Acad Sci U S A 96:13409–13414
CAS Article PubMed PubMed Central Google Scholar
Yamamoto K, Sato T, Matsui T et al (2007) Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6α and XBP1. Dev Cell 13:365–376. https://doi.org/10.1016/j.devcel.2007.07.018
CAS Article PubMed Google Scholar
Yang W, Hinnebusch AG (1996) Identification of a regulatory subcomplex in the guanine nucleotide exchange factor eIF2B that mediates inhibition by phosphorylated eIF2. Mol Cell Biol 16:6603–6616
CAS Article PubMed PubMed Central Google Scholar
Yang M, Vousden KH (2016) Serine and one-carbon metabolism in cancer. Nat Rev Cancer 16:650–662. https://doi.org/10.1038/nrc.2016.81
CAS Article PubMed Google Scholar
Yang L, Zhang B, Toku K et al (2000) Improvement of the viability of cultured rat neurons by the non-essential amino acids L-serine and glycine that upregulates expression of the anti-apoptotic gene product Bcl-w. Neurosci Lett 295:97–100. https://doi.org/10.1016/S0304-3940(00)01597-4
CAS Article PubMed Google Scholar

Download references

Author information

J. S. Metcalf and R. A. Dunlop contributed equally to this work.

Authors and Affiliations

Brain Chemistry Labs, The Institute for Ethnomedicine, Jackson, 83001, WY, USA
J. S. Metcalf, R. A. Dunlop, J. T. Powell, S. A. Banack & P. A. Cox

Authors

J. S. Metcalf
View author publications
You can also search for this author in PubMed Google Scholar
R. A. Dunlop
View author publications
You can also search for this author in PubMed Google Scholar
J. T. Powell
View author publications
You can also search for this author in PubMed Google Scholar
S. A. Banack
View author publications
You can also search for this author in PubMed Google Scholar
P. A. Cox
View author publications
You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. A. Cox.

Ethics declarations

Competing Interests

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

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Metcalf, J.S., Dunlop, R.A., Powell, J.T. et al. L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential. Neurotox Res 33, 213–221 (2018). https://doi.org/10.1007/s12640-017-9814-x

Download citation

Received: 02 February 2017
Revised: 25 August 2017
Accepted: 05 September 2017
Published: 19 September 2017
Issue Date: January 2018
DOI: https://doi.org/10.1007/s12640-017-9814-x

Keywords

L-serine
Alzheimer’s Disease
Therapy
Neuroprotection
ALS
Neurodegeneration