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Neuroinflammation in Parkinson’s Disease

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Abstract

During the last two decades, a wealth of animal and human studies has implicated inflammation-derived oxidative stress and cytokine-dependent neurotoxicity in the progressive degeneration of the dopaminergic nigrostriatal pathway, the hallmark of Parkinson’s disease (PD). In this review, we discuss the various hypotheses regarding the role of microglia and other immune cells in PD pathogenesis and progression, the inflammatory mechanisms implicated in disease progression from pre-clinical and clinical studies, the recent evidence that systemic inflammation can trigger microglia activation in PD-relevant central nervous system regions, the synergism between gene products linked to parkinsonian phenotypes (α-synuclein, parkin, Nurr1, and regulator of G-protein signaling-10) and neuroinflammation in promoting neurodegeneration of the nigrostriatal pathway, and the latest update on meta-analysis of epidemiological studies on the risk-lowering effects of anti-inflammatory drug regimens.

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Abbreviations

CNS:

Central nervous system

RNS/ROS:

Reactive nitrogen species/reactive oxygen species

6-OHDA:

6-Hydroxydopamine

TNF:

Tumor necrosis factor

IL-1β:

Interleukin-1beta

IL-6:

Interleukin-6

IFNγ:

Interferon gamma

TGF-β:

Transforming growth factor beta

BBB:

Blood-brain barrier

SNpc:

Substantia nigra pars compacta

LPS:

Lipopolysaccharide

PD:

Parkinson’s disease

AD:

Alzheimer’s disease

DA:

Dopaminergic

VTA:

Ventral tegmental area

NO:

Nitric oxide

LBs:

Lewy bodies

PET:

Positron emission tomography

alpha-MPT:

Alpha-methyl-p-tyrosine

RGS10:

Regulator of G-protein signaling-10

COX-1:

Cyclooxygenase-1

COX-2:

Cyclooxygenase-2

NSAIDs:

Nonsteroidal anti-inflammatory drugs

MPTP:

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

iNOS:

Inducible nitric oxide synthase

NF-κB:

Nuclear factor kappa beta

NBD:

NF-κB essential modifier (NEMO)-binding domain

IKKα:

IκB Kinase α subunit

IKKβ:

IκB Kinase β subunit

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Authors and Affiliations

  1. Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    Jae-Kyung Lee, Thi Tran & Malú G. Tansey

  2. Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA, 30322, USA

    Malú G. Tansey

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  1. Jae-Kyung Lee
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  2. Thi Tran
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Lee, JK., Tran, T. & Tansey, M.G. Neuroinflammation in Parkinson’s Disease. J Neuroimmune Pharmacol 4, 419–429 (2009). https://doi.org/10.1007/s11481-009-9176-0

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