Abstract
Parkinson's disease (PD) is a neurodegenerative disorder marked primarily by motor symptoms such as rigidity, bradykinesia, postural instability and resting tremor associated with dopaminergic neuronal loss in the Substantia Nigra pars compacta (SNpc) and deficit of dopamine in the basal ganglia. These motor symptoms can be preceded by pre-motor symptoms whose recognition can be useful to apply different strategies to evaluate risk, early diagnosis and prevention of PD progression. Although clinical characteristics of PD are well defined, its pathogenesis is still not completely known, what makes discoveries of therapies capable of curing patients difficult to be reached. Several theories about the cause of idiopathic PD have been investigated and among them, the key role of inflammation, microglia and the inflammasome in the pathogenesis of PD has been considered. In this review, we describe the role and relation of both the inflammasome and microglial activation with the pathogenesis, symptoms, progression and the possibilities for new therapeutic strategies in PD.
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Abbreviations
- [18F]-FEPPA:
-
[18F]-Radiolabelled phenoxyanilide
- 6-OHDA:
-
6-Hydroxydopamine
- AIM2:
-
Absent in melanoma 2
- ALR:
-
AIM2-like receptor
- ASC:
-
Caspase activating adapter protein
- BDNF:
-
Brain-derived neurotrophic factor
- BRCC3:
-
Lys-63-specific deubiquitinase
- CARD:
-
N-terminal caspase recruitment
- CCL2:
-
Chemokine ligand 2
- CCL5:
-
Chemokine ligand 5
- CNS:
-
Central nervous system
- COX-2:
-
Cyclooxygenase-2
- CX3CL1:
-
Chemokine ligand 1
- CXCL8:
-
Chemokine ligand 8
- DAMPs:
-
Damage-associated molecular pattern
- PD:
-
Parkinson's disease
- DSP-4:
-
N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine
- EMPs:
-
Erythromyeloid precursors
- ERK 1/2:
-
Extracellular signal-regulated kinase
- FIND:
-
Function to find domain
- GDNF:
-
Glia-derived neurotrophic factor
- HEK293:
-
Human embryonic kidney 293 cells
- Iba1:
-
Ionized calcium-binding adaptor molecule 1
- IL-18:
-
Interleukin-18
- IL-1β :
-
Interleukin-1β
- IL-6:
-
Interleukin-6
- IL1-R1:
-
Interleukin-1 receptor 1
- IEA-NLRC4:
-
Infantile enterocolitis associated with NLRC4
- JNK:
-
C-Jun NH2-terminal kinase
- l-dopa:
-
l-3,4-Dihydroxyphenylalanine
- LPS:
-
Lipopolysaccharide
- LRR:
-
Leucine-rich repeats
- MAL/TIRAP:
-
MyD88 adaptor-like protein/TIR-containing adaptor protein
- MAS:
-
Macrophage activation syndrome
- MAO-B:
-
Monoamine oxidase B
- MAPK:
-
Mitogen-activated protein kinases
- MD2:
-
Myeloid differentiation protein-2
- MPTP:
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- MyD88:
-
Myeloid differentiation protein
- NACHT:
-
Nucleotide-binding and oligomerization
- NF-κB:
-
Factor nuclear kappa B
- NLRP3:
-
NOD-like receptor protein 3
- NLRs:
-
NOD-like receptors
- NO:
-
Nitric oxide
- PAMPs:
-
Pathogen-associated molecular pattern
- PET:
-
Positron emission tomography
- Pro-IL-1β :
-
Pro-interleukin-1β
- PRRs:
-
Pattern-recognition receptors
- PYD:
-
Pyrin domains
- ROS:
-
Reactive oxygen species
- SNpc:
-
Substantia nigra pars compacta
- TIR:
-
Toll/interleukin-1
- TNF-α :
-
Tumor necrosis factor-α
- TNFR1:
-
Tumor necrosis factor receptor 1
- TNFR12:
-
Tumor necrosis factor receptor 2
- TLR:
-
Toll-like receptor
- TSPO:
-
Translocating protein
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Acknowledgements
F.M.A. thanks Coordenação de Apoio de Pessoal de Nível Superior (PDSE -47/2017) for its support; L.C.B. thanks the Spanish Ministry of Science, Innovation and Universities (FPU 18/02549) for its support; M.T.H. thanks the Federación Española de Parkinson (FIS PI13 01293) and the Fundación Séneca (19540/PI/14) for its support; V.D.A.S and S.L.C. thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ E. Universal/2018—429127/2018-9; and CNPQ—Research Fellowship) and Fundação de Amparo à Pesquisa do Estado da Bahia (JCB0057/2016) for its support.
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Both FMA, LC, and EF performed literature research and wrote the review. SLC, VDAS and MTH helped with the conceptualization of the review and performed literature research.
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de Araújo, F.M., Cuenca-Bermejo, L., Fernández-Villalba, E. et al. Role of Microgliosis and NLRP3 Inflammasome in Parkinson’s Disease Pathogenesis and Therapy. Cell Mol Neurobiol 42, 1283–1300 (2022). https://doi.org/10.1007/s10571-020-01027-6
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DOI: https://doi.org/10.1007/s10571-020-01027-6