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The Role of Inflammatory and Oxidative Stress Mechanisms in the Pathogenesis of Parkinson’s Disease: Focus on Astrocytes

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Abstract

Neuroinflammation plays a key role in the pathogenesis of Parkinson’s disease (PD). Epidemiologic, animal, human, and therapeutic studies support the role of oxidative stress and inflammatory cascade in initiation and progression of PD. In Parkinson’s disease pathophysiology, activated glia affects neuronal injury and death through production of neurotoxic factors like glutamate, S100B, tumor necrosis factor alpha (TNF-α), prostaglandins, and reactive oxygen and nitrogen species. As disease progresses, inflammatory secretions engage neighboring cells, including astrocytes and endothelial cells, resulting in a vicious cycle of autocrine and paracrine amplification of inflammation leading to neurodegeneration. The exact mechanism of these inflammatory mediators in the disease progression is still poorly understood. In this review, we highlight and discuss the mechanisms of oxidative stress and inflammatory mediators by which they contribute to the disease progression. Particularly, we focus on the altered role of astroglial cells that presumably initiate and execute dopaminergic neurodegeneration in PD. In conclusion, we focus on the molecular mechanism of neurodegeneration, which contributes to the basic understanding of the role of neuroinflammation in PD pathophysiology.

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Abbreviations

NGF:

Nerve growth factor

GDNF:

Glial cell line-derived neurotrophic factor

MANF:

Mesencephalic astrocyte-derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

TNF-α:

Tumor necrosis factor-α

NF-κB:

Nuclear factor kappa-B

COX-2:

Cyclooxygenase-2

GFAP:

Glial fibrillary acidic protein

CHOP:

C/EBP homologous protein 10

iNOS:

Inducible nitric oxide synthase

IL-1α:

Interleukin-1α

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

P-p38 MAPK:

Phosphorylated p38 mitogen-activated protein kinase

NO:

Nitrite

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Acknowledgments

Lab space and facilities provided by Dr. Anil Mishra at the School of Medicine, Division of Gastroenterology and Liver Disease, Case Western Reserve University, Cleveland, OH, USA, is gratefully acknowledged.

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  1. Division of Gastroenterology and Liver Diseases, Case Western Reserve University, School of Medicine, 2109 Adelbert Rd., BRB 501, Cleveland, OH, 44106, USA

    Rituraj Niranjan

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Niranjan, R. The Role of Inflammatory and Oxidative Stress Mechanisms in the Pathogenesis of Parkinson’s Disease: Focus on Astrocytes. Mol Neurobiol 49, 28–38 (2014). https://doi.org/10.1007/s12035-013-8483-x

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  • DOI: https://doi.org/10.1007/s12035-013-8483-x

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