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NF-κB-Mediated Neuroinflammation in Parkinson’s Disease and Potential Therapeutic Effect of Polyphenols

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Abstract

Different animal and human studies from last two decades in the case of Parkinson’s disease (PD) have concentrated on oxidative stress due to increased inflammation and cytokine-dependent neurotoxicity leading to induction of dopaminergic (DA) degeneration pathway in the nigrostriatal region. Chronic inflammation, the principle hallmark of PD, forms the basis of neurodegeneration. Aging in association with activation of glia due to neuronal injury, perhaps because of immune alterations and genetic predispositions, leads to deregulation of inflammatory pathways premising the onset of PD. A family of inducible transcription factors, nuclear factor-κB (NF-κB), is found to show expression in various cells and tissues, such as microglia, neurons, and astrocytes which play an important role in activation and regulation of inflammatory intermediates during inflammation. Both canonical and non-canonical NF-κB pathways are involved in the regulation of the stimulated cells. During the prodromal/asymptomatic stage of age-associated neurodegenerative diseases (i.e., PD and AD), chronic neuroinflammation may act silently as the driver of neuronal dysfunction. Though research has provided an insight over age-related neurodegeneration in PD, elaborative role of NF-κB in neuroinflammation is yet to be completely understood and thus requires more investigation. Polyphenols, a group of naturally occurring compound in medicinal plants, have gained attention because of their anti-oxidative and anti-neuroinflammatory properties in neurodegenerative diseases. In this aspect, this review highlights the role of NF-κB and the possible therapeutic roles of polyphenols in NF-κB-mediated neuroinflammation in PD.

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Abbreviations

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

PD:

Parkinson’s disease

DA:

Dopaminergic

TNF-α:

Tumor necrosis factor

MPTPq:

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

CNS:

Central nervous system

SNpc:

Substantia nigra pars compacta

CGA:

Chlorogenic acid

ROS:

Reactive oxygen species

TH:

Tyrosine hydroxylase

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Acknowledgments

SSS, SNR, HB, WZ, and ASR are sincerely thankful to ICMR, DBT, and BHU, India, for their respective fellowship. The present study was not supported by any funding agencies.

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  1. Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    Saumitra Sen Singh, Sachchida Nand Rai, Hareram Birla, Walia Zahra, Aaina Singh Rathore & Surya Pratap Singh

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  1. Saumitra Sen Singh
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SSS planed the work and drafted the manuscript; SNR, WZ, and ASR helped in the manuscript preparation; HB designed and has drawn the figures and pathway; and SPS guided throughout the manuscript.

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Singh, S.S., Rai, S.N., Birla, H. et al. NF-κB-Mediated Neuroinflammation in Parkinson’s Disease and Potential Therapeutic Effect of Polyphenols. Neurotox Res 37, 491–507 (2020). https://doi.org/10.1007/s12640-019-00147-2

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