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Emerging perspectives on mitochondrial dysfunctioning and inflammation in epileptogenesis

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Inflammation Research Aims and scope Submit manuscript

Abstract

Introduction

Mitochondrial dysfunction is a common denominator of neuroinflammation recognized by neuronal oxidative stress-mediated apoptosis that is well recognized by common intracellular molecular pathway-interlinked neuroinflammation and mitochondrial oxidative stress, a feature of epileptogenesis. In addition, the neuronal damage in the epileptic brain corroborated the concept of brain injury-mediated neuroinflammation, further providing an interlink between inflammation, mitochondrial dysfunction, and oxidative stress in epilepsy.

Materials and methods

A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to provide evidence of preclinical and clinically used drugs targeting such nuclear, cytosolic, and mitochondrial proteins suggesting that the correlation of mechanisms linked to neuroinflammation has been elucidated in the current review. Despite that, the evidence of elevated levels of inflammatory mediators and pro-apoptotic protein levels can provide the correlation of inflammatory responses often concerned with hyperexcitability attributing to the fact that mitochondrial redox mechanisms and higher susceptibilities to neuroinflammation result from repetitive recurring epileptic seizures. Therefore, providing an understanding of seizure-induced pathological changes read by activating neuroinflammatory cascades like NF-kB, RIPK, MAPK, ERK, JNK, and JAK-STAT signaling further related to mitochondrial damage promoting hyperexcitability.

Conclusion

The current review highlights the further opportunity for establishing therapeutic interventions underlying the apparent correlation of neuroinflammation mediated mitochondrial oxidative stress might contribute to common intracellular mechanisms underlying a future prospective of drug treatment targeting mitochondrial dysfunction linked to the neuroinflammation in epilepsy.

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Abbreviations

ERK:

Extracellular regulated kinase

NF-κB:

Nuclear factor-kappa light chain enhancer of activated B cells

JAK–STAT:

Janus kinases signal transducer and activator of transcription proteins

MAPK:

Mitogen-activated protein kinases

P38:

P38 MAP KINASE

PPARs:

Peroxisome proliferator-activated receptors

MPTP:

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

AMPK:

AMP-activated protein kinase

SIRT1:

Silent mating type information regulation 2 homolog

PGC-1-alpha:

Peroxisome proliferator-activated receptor-γ

COX-2:

Cyclooxygenase2

ASK-1:

Apoptosis signal-regulating kinase-1

TNF α:

Tumor necrosis factor alpha

IL-1:

Interleukin-1

INOS:

Inducible nitric oxide synthase

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

UCP2:

Uncoupling protein 2

CCL2:

Chemokine (C–C motif) ligand 2

MnSOD:

Manganese-dependent superoxide dismutase

DNA:

Deoxyribonucleic acid

NAD:

Nicotinamide adenine dinucleotide

FOXO:

Forkhead box transcription factors

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Acknowledgements

The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India for providing the necessary facilities to carry out the research work.

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  1. Chitkara College of Pharmacy, Chitkara University, Punjab, 140401, India

    Shareen Singh & Thakur Gurjeet Singh

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Conceptualization: conceived and designed the experiments: TGS. Analyzed the data: SS and TGS. Wrote the manuscript: SS. Editing of the manuscript: TGS; critically reviewed the article: TGS. All authors read and approved the final manuscript.

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Singh, S., Singh, T.G. Emerging perspectives on mitochondrial dysfunctioning and inflammation in epileptogenesis. Inflamm. Res. 70, 1027–1042 (2021). https://doi.org/10.1007/s00011-021-01511-9

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