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The role of inflammation in sporadic and familial Parkinson’s disease

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Abstract

The etiology of Parkinson’s disease (PD) is complex and most likely involves numerous environmental and heritable risk factors. Interestingly, many genetic variants, which have been linked to familial forms of PD or identified as strong risk factors, also play a critical role in modulating inflammatory responses. There has been considerable debate in the field as to whether inflammation is a driving force in neurodegeneration or simply represents a response to neuronal death. One emerging hypothesis is that inflammation plays a critical role in the early phases of neurodegeneration. In this review, we will discuss emerging aspects of both innate and adaptive immunity in the context of the pathogenesis of PD. We will highlight recent data from genetic and functional studies that strongly support the theory that genetic susceptibility plays an important role in modulating immune pathways and inflammatory reactions, which may precede and initiate neuronal dysfunction and subsequent neurodegeneration. A detailed understanding of such cellular and molecular inflammatory pathways is crucial to uncover pathogenic mechanisms linking sporadic and hereditary PD and devise tailored neuroprotective interventions.

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Fig. 1
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Abbreviations

AD:

Alzheimer’s disease

APC:

Antigen-presenting cell

α-syn:

α-Synuclein

CNS:

Central nervous system

COX:

Cyclooxygenase

CD:

Crohn’s disease

DA:

Dopaminergic

EOPD:

Early onset Parkinson’s disease

FBXO7:

F-box protein 7

GBA:

Glucocerebrosidase

GD:

Gaucher’s disease

GCase:

Glucocerebrosidase

GWAS:

Genome wide association study

HLA:

Human leukocyte antigen

IBD:

Inflammatory bowel disease

IL-1β:

Interleukin-1beta

LB:

Lewy bodies

LN:

Lewy neurites

LPS:

Lipopolysaccharide

LRRK2:

Leucine-rich repeat kinase 2

MPTP:

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

MS:

Multiple sclerosis

NO:

Nitric oxide

NR:

Nuclear receptor

PD:

Parkinson’s disease

PLA2G6:

Phospholipase A2 group VI

PPAR:

Peroxisome proliferator-activated receptor

ROS:

Reactive oxygen species

SN:

Substantia nigra

TH:

Tyrosine hydroxylase

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-alpha

VIP:

Vasoactive intestinal peptide

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Acknowledgments

This work was supported by grants from the German Research Council and Marie Curie Career Integration Grant, and by a Research Grant from the Alexander Von Humboldt Foundation.

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Deleidi, M., Gasser, T. The role of inflammation in sporadic and familial Parkinson’s disease. Cell. Mol. Life Sci. 70, 4259–4273 (2013). https://doi.org/10.1007/s00018-013-1352-y

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