Image_3_Therapeutic Effect of Modulating TREM-1 via Anti-inflammation and Autophagy in Parkinson’s Disease.TIF
Chien-Wei Feng
Nan-Fu Chen
Chun-Sung Sung
Hsiao-Mei Kuo
San-Nan Yang
Chien-Liang Chen
Han-Chun Hung
Bing-Hung Chen
Zhi-Hong Wen
Wu-Fu Chen
10.3389/fnins.2019.00769.s003
https://frontiersin.figshare.com/articles/figure/Image_3_Therapeutic_Effect_of_Modulating_TREM-1_via_Anti-inflammation_and_Autophagy_in_Parkinson_s_Disease_TIF/9273266
<p>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.</p>
2019-08-06 15:27:31
TREM-1
Parkinson’s disease
neuroinflammation
autophagy
zebrafish
rat