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Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors

  • Sumit Barua
  • Jong Youl Kim
  • Jae Young Kim
  • Jae Hwan Kim
  • Jong Eun LeeEmail author
Review Paper
  • 91 Downloads

Abstract

The central nervous system (CNS) is the most injury-prone part of the mammalian body. Any acute or chronic, central or peripheral neurological disorder is related to abnormal biochemical and electrical signals in the brain cells. As a result, ion channels and receptors that are abundant in the nervous system and control the electrical and biochemical environment of the CNS play a vital role in neurological disease. The N-methyl-d-aspartate receptor, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor, kainate receptor, acetylcholine receptor, serotonin receptor, α2-adrenoreceptor, and acid-sensing ion channels are among the major channels and receptors known to be key components of pathophysiological events in the CNS. The primary amine agmatine, a neuromodulator synthesized in the brain by decarboxylation of l-arginine, can regulate ion channel cascades and receptors that are related to the major CNS disorders. In our previous studies, we established that agmatine was related to the regulation of cell differentiation, nitric oxide synthesis, and murine brain endothelial cell migration, relief of chronic pain, cerebral edema, and apoptotic cell death in experimental CNS disorders. In this review, we will focus on the pathophysiological aspects of the neurological disorders regulated by these ion channels and receptors, and their interaction with agmatine in CNS injury.

Keywords

Agmatine Ion channels Receptors Neurodegenerative disease Receptor blockade 

Abbreviations

CNS

Central nervous system

PNS

Peripheral nervous system

AD

Alzheimer’s disease

PD

Parkinson’s disease

HD

Huntington’s disease

ADC

Arginine decarboxylase

ROS

Reactive oxygen species

NF-κB

Nuclear factor kappa B

TBI

Traumatic brain injury

NO

Nitric oxide

SCI

Spinal cord injury

BMP

Bone morphogenetic protein

Amyloid-beta

Nrf2

Nuclear factor (erythroid derived 2)-like 2

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MES

Maximal electroshock seizures

PTZ

Pentylenetetrazole

NMDAR

N-Methyl-d-aspartate receptor

AMPAR

α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor

NOS

Nitric oxide synthase

KAR

Kainite receptor

GPCR

G protein-coupled receptor

CDS

Clonidine displacing substance

AChR

Acetylcholine

mAChR

Muscarinic acetylcholine receptor

nAChR

Nicotinic acetylcholine receptor

5-HT

5-Hydroxytryptamine

VDCC

Voltage-dependent calcium channel

LVA

Low-voltage activated

HVA

High-voltage activated

ENaC/DEG

Epithelial Na+ channel/degenerin

ASIC

Acid-sensing ion channel

EL/IL

Extracellular/intracellular loops

Notes

Acknowledgements

This study was supported by National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (2017R1A2B2005350).

Author Contributions

JEL provided concept, design and overall supervision of this study. SB, JYK1 contributed in the writing and drawing. JYK2, JHK and JEL participated in the discussion and revision. All authors approved and agreed to be accountable for all aspects of the work.

Funding

This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (2017R1A2B2005350).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no competing interests.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of AnatomyYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Brain Korea 21 PLUS Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea
  3. 3.Brain Research InstituteYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Center for Neuroscience Imaging Research (CNIR), Insititute for Basic ScienceSungkyunkwan UniversitySeoulRepublic of Korea

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