Human TH blocking peptide

This study aimed to explore the detailed molecular mechanism and biomarkers in spinal cord injury (SCI). Gene expression profiles of GSE125630 were downloaded from the Gene Expression Omnibus (GEO) database, and comprised 14 spinal cord tissues, including contusion SCI group (n = 6, unexercised), complete transection group (n = 4, unexercised), and uninjured control group (n = 4, unexercised). Differentially expressed gene (DEG) and time-series gene investigations, functional enrichment analysis, protein-protein interaction (PPI) network construction, characteristic gene-related disease analysis, and TF-target gene interaction studies were performed. A total of 122 DEGs and 409 DEGs were respectively identified in contusion SCI versus control group and complete transection versus control group, respectively. The PPI network investigated 16 characteristic genes including corticotropin-releasing hormone (CRH), tyrosine hydroxylase (TH), and neurotensin (NTS). These genes were mainly enriched in functions involving response to ethanol, corticosterone, and estradiol. Eventually, a TF-target gene interaction network was constructed with nine TFs [including activating transcription factor 3 (ATF3)] and 10 characteristic genes. The results indicate that regulation of osteoblast differentiation and positive regulation of the BMP signaling pathway may be suppressed in the process of SCI. TH may play a pivotal role in the progression of SCI. In addition, DEGs such as CRH and NTS may be novel targets for SCI therapy.

Dopaminergic functions are important for various biological activities, and their impairment leads to neurodegeneration, a hallmark of Parkinson's disease (PD). Chronic manganese (Mn) exposure causes the neurological disorder manganism, presenting symptoms similar to those of PD. Emerging evidence has linked the transcription factor RE1-silencing transcription factor (REST) to PD and also Alzheimer's disease. But REST's role in dopaminergic neurons is unclear. Here, we investigated whether REST protects dopaminergic neurons against Mn-induced toxicity and enhances expression of the dopamine-synthesizing enzyme tyrosine hydroxylase (TH). We report that REST binds to RE1 consensus sites in the TH gene promoter, stimulates TH transcription, and increases TH mRNA and protein levels in dopaminergic cells. REST binding to the TH promoter recruited the epigenetic modifier cAMP-response element-binding protein?binding protein/p300 and thereby up-regulated TH expression. REST relieved Mn-induced repression of TH promoter activity, mRNA, and protein levels and also reduced Mn-induced oxidative stress, inflammation, and apoptosis in dopaminergic neurons. REST reduced Mn-induced proinflammatory cytokines, including tumor necrosis factor ?, interleukin 1? (IL-1?), IL-6, and interferon ?. Moreover, REST inhibited the Mn-induced proapoptotic proteins Bcl-2?associated X protein (Bax) and death-associated protein 6 (Daxx) and attenuated an Mn-induced decrease in the antiapoptotic proteins Bcl-2 and Bcl-xL. REST also enhanced the expression of antioxidant proteins, including catalase, NF-E2?related factor 2 (Nrf2), and heme oxygenase 1 (HO-1). Our findings indicate that REST activates TH expression and thereby protects neurons against Mn-induced toxicity and neurological disorders associated with dopaminergic neurodegeneration.