PUBLICATION
Therapeutic Effect of Modulating TREM-1 via Anti-inflammation and Autophagy in Parkinson's Disease
- Authors
- Feng, C.W., Chen, N.F., Sung, C.S., Kuo, H.M., Yang, S.N., Chen, C.L., Hung, H.C., Chen, B.H., Wen, Z.H., Chen, W.F.
- ID
- ZDB-PUB-190826-6
- Date
- 2019
- Source
- Frontiers in neuroscience 13: 769 (Journal)
- Registered Authors
- Keywords
- Parkinson’s disease, TREM-1, autophagy, neuroinflammation, rat, zebrafish
- MeSH Terms
- none
- PubMed
- 31440123 Full text @ Front. Neurosci.
Citation
Feng, C.W., Chen, N.F., Sung, C.S., Kuo, H.M., Yang, S.N., Chen, C.L., Hung, H.C., Chen, B.H., Wen, Z.H., Chen, W.F. (2019) Therapeutic Effect of Modulating TREM-1 via Anti-inflammation and Autophagy in Parkinson's Disease. Frontiers in neuroscience. 13:769.
Abstract
Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases, and neuroinflammation has been identified as one of its key pathological characteristics. Triggering receptors expressed on myeloid cells-1 (TREM-1) amplify the inflammatory response and play a role in sepsis and cancer. Recent studies have demonstrated that the attenuation of TREM-1 activity produces cytoprotective and anti-inflammatory effects in macrophages. However, no study has examined the role of TREM-1 in neurodegeneration. We showed that LP17, a synthetic peptide blocker of TREM-1, significantly inhibited the lipopolysaccharide (LPS)-induced upregulation of proinflammatory cascades of inducible nitric oxide synthase (iNOS), cyclooxygenase-2, and nuclear factor-kappa B. Moreover, LP17 enhanced the LPS-induced upregulation of autophagy-related proteins such as light chain-3 and histone deacetylase-6. We also knocked down TREM-1 expression in a BV2 cell model to further confirm the role of TREM-1. LP17 inhibited 6-hydroxydopamine-induced locomotor deficit and iNOS messenger RNA expression in zebrafish. We also observed therapeutic effects of LP17 administration in 6-hydroxydopamine-induced PD syndrome using a rat model. These data suggest that the attenuation of TREM-1 could ameliorate neuroinflammatory responses in PD and that this neuroprotective effect might occur via the activation of autophagy and anti-inflammatory pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping