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The potential roles of amino acids and their major derivatives in the management of multiple sclerosis

Abstract

Recently, we reviewed the important role of carbohydrates and lipids metabolism in different clinical aspects of multiple sclerosis (MS) disease. In the current paper, we aimed to review the contribution of amino acids and their major derivatives to different clinical outcomes of the disease, including etiology, pathogenesis, diagnosis, prognosis, and treatment. In this line, Thr (threonine), Phe (phenylalanine), Glu (glutamate), Trp (tryptophan), and Sero (serotonin) are the main examples of biomolecules that have been suggested for MS therapy. It has been concluded that different amino acids and their derivatives might be considered prominent tools for the clinical management of MS disease.

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Abbreviations

3-HAA:

3-hydroxyanthranilic acid

3-HK:

3-hydroxykynurenine

5-HIAA:

5- hydroxyindoleacetic acid

5-HTP:

5-hydroxytryptophan

5-MTHF:

5‐methyltetrahydrofolate

AA:

Amino acid

AhRs:

Aryl hydrocarbon receptors

Ala:

Alanine

ARG 1:

Arginase 1

ARG:

Arginase

Arg:

L-arginine

Asn:

Asparagine

Asp:

Aspartate

BCAAs:

Branched-chain amino acids

Cho:

Choline

CIS:

Clinically isolated syndrome

CNS:

Central nervous system

COMT:

Catechol-o-methyl transferase

CPS1:

Carbamoyl phosphate synthetase 1

CSF:

Cerebrospinal fluid

Cys:

Cysteine

DA:

Dopamine

DAO:

Diamine oxidase

DCs:

Dendritic cells

DR D3:

Dopaminergic receptor D3

DR D5:

Dopaminergic receptor D5

EAE:

Experimental autoimmune encephalomyelitis

EP:

Epinephrine

GABA:

Gamma-aminobutyric acid

GAD:

Glutamate decarboxylase

GDH:

Glutamate dehydrogenase

Gln:

Glutamine

Glu:

Glutamate

Gly:

Glycine

GS:

Glutamine synthetase

GSH:

Glutathione, L-γ-glutamyl-L-cysteinyl glycine

H4R:

Histamine H4 receptor

Hcy:

Homocysteine

HDC:

L-histidine decarboxylase

His:

Histidine

HMT:

Histamine-N-methyltransferase

HNMT:

Histamine-N-methyltransferase

HVA:

Homovanillic acid

IAA:

Indoleacetic acid

IDO:

Indole amine dioxygenase

Ile:

Isoleucine

iNOS:

Inducible nitric oxide synthase

KAT:

Kynurenine aminotransferase

Kyn/trp ratio:

Kynurenine/tryptophan ratio

Kyn:

Kynurenine

Kyna:

Kynurenic acid

Leu:

Leucine

Lys:

Lysine

MAO:

Monoamine oxidase

MAOA:

Monoamine oxidase type A

MAOB:

Monoamine oxidase type B

MAT:

Methionine adenosyl transferase

Mel:

Melatonin

Met:

Methionine

MHPG:

3-methoxy-4-hydroxyphenylglycol

mRNA:

Messenger RNA

MS:

Multiple sclerosis

MTHF:

Methylene-tetrahydrofolate

MTHFR:

Methylenetetrahydrofolate reductase

MTNR1B:

Melatonin receptor 1B

NA:

Noradrenaline

NAD + :

Nicotinamide adenine dinucleotide

NAS:

N-acetyl serotonin

NE:

Norepinephrine

NKCs:

Natural killer cells

NO:

Nitric oxide

NOS:

Nitric oxide synthase

OTC:

Ornithine transcarboxylase

PBMCs:

Peripheral blood mononuclear cells

Pcr:

Phosphocreatine

Phe:

Phenylalanine

PNMT:

Phenylethanolamine N-methyltransferase

PQ:

Picolinic acid

Pro:

Proline

QA/kyn ratio:

Quinolinic acid/kynurenine ratio

QA:

Quinolinic acid

RBCs:

Red blood cells

RRMS:

Relapse remitting multiple sclerosis

SAM:

S- adenosyl methionine

Ser:

Serine

Sero/mel pathway:

Serotonin/melatonin pathway

Sero:

Serotonin

SHMT:

Serine hydroxymethyltransferase

SPMS:

Secondary progressive multiple sclerosis

TCA:

Tricarboxylic cycle

Teffs:

T effector cells

Th-17:

T helper 17

Th1:

T helper 1

Th2:

T helper 2

TH:

Tyrosine hydroxylase

THF:

Tetrahydrofolate

Thr:

Threonine

TPH:

Tryptophan hydroxylase

Tregs:

T regulatory cells

Trp:

Tryptophan

Tyr:

Tyrosine

Val:

Valine

VMA:

Vanillylmandelic acid

Α-KA:

Alpha- ketoacid

α2A-AR:

α2A-adrenoceptors

References

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Acknowledgements

The authors are thankful from Mr. Seyyed Mortaza Haghgoo for his useful comments on the current paper.

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Correspondence to Mohammad Sajad Emami Aleagha.

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The authors declare that there is no conflict of interests.

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Pashaei, S., Yarani, R., Mohammadi, P. et al. The potential roles of amino acids and their major derivatives in the management of multiple sclerosis. Amino Acids 54, 841–858 (2022). https://doi.org/10.1007/s00726-022-03162-4

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  • DOI: https://doi.org/10.1007/s00726-022-03162-4

Keywords

  • Amino acids
  • Metabolic pathways
  • Multiple sclerosis