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

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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.

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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

Aβ:

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

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Acknowledgements

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

Funding

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

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  1. Sumit Barua and Jong Youl Kim have contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-gu, Seoul, 03722, Republic of Korea

    Sumit Barua, Jong Youl Kim, Jae Young Kim & Jong Eun Lee

  2. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50 Yonsei-Ro, Seoul, 03722, Republic of Korea

    Jong Eun Lee

  3. Brain Research Institute, Yonsei University College of Medicine, 50 Yonsei-Ro, Seoul, 03722, Republic of Korea

    Jong Eun Lee

  4. Center for Neuroscience Imaging Research (CNIR), Insititute for Basic Science, Sungkyunkwan University, Seoul, Republic of Korea

    Jae Hwan Kim

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  1. Sumit Barua
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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.

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Correspondence to Jong Eun Lee.

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Barua, S., Kim, J.Y., Kim, J.Y. et al. Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors. Neurochem Res 44, 735–750 (2019). https://doi.org/10.1007/s11064-018-02712-1

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