Therapeutic Effect of Modulating TREM-1 via Anti-inflammation and Autophagy in Parkinson's Disease

• Published in: Frontiers in neuroscience Vol. 13; p. 769
• Main Authors: Feng, Chien-Wei, Chen, Nan-Fu, Sung, Chun-Sung, Kuo, Hsiao-Mei, Yang, San-Nan, Chen, Chien-Liang, Hung, Han-Chun, Chen, Bing-Hung, Wen, Zhi-Hong, Chen, Wu-Fu
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 02.08.2019; Frontiers Media S.A
• Subjects: 6-Hydroxydopamine; Age; Autophagy; Cyclooxygenase-2; Cytokines; Disease; Experiments; Gene expression; Histone deacetylase; Immunoglobulins; Inflammation; Laboratory animals; Lipopolysaccharides; Macrophages; Movement disorders; Myeloid cells; Neurodegeneration; Neurodegenerative diseases; neuroinflammation; Neuroprotection; Neuroscience; Nitric oxide; Nitric-oxide synthase; Parkinson's disease; Peptides; Phagocytosis; rat; Sepsis; Studies; TREM-1; zebrafish; Grand Island New York; St Louis Missouri; United States > US; Taiwan; TREM-1; autophagy; zebrafish; rat; neuroinflammation; Parkinson’s disease
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2019.00769

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.