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.
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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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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DOI: https://doi.org/10.1007/s00018-013-1352-y