Tyrosine Hydroxylase (Phospho-Ser31) ELISA Kit

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the ventral midbrain dopaminergic neurons, resulting in motor defects mainly tremor, rigidity, and bradykinesia along with a wide array of non-motor symptoms. The current study is focused on determining the potential druggable targets of PD by consolidating gene expression profiling and network methodology. Initially, the differentially expressed genes were established from which the central network was constructed by assimilating the interacting partners. Investigating the topological parameters of the network, the genesSYT1,CXCR4,CDC42,KIT,RET,DRD2,NTN1,PRKACB,KDR,NR4A2,SLC18A2,CCK,TH,KCNJ6, andTAC1were identified as the hub genes and can be explored as potential candidate genes for PD therapeutics. Gene ontology and cluster analysis of the hub genes has provided further insights about the pathophysiology of the disease. Among the hub genes,PRKACBis observed in relatively all the enriched pathways which are modulated by G protein-coupled receptors through protein kinases. Further, we noticedSYT1as a novel biomarker for PD. Moreover, the regulatory network was constructed with the hub genes as seed nodes with associated transcription factors (TFs) and microRNA (miRNAs). In this analysis, we identified MYC as the major TF and the miRNAsmiR-21,miR-155,miR-7, andmiR26A1have a significant role in modulating the hub genes. Briefly, these significant hub genes and their enriched pathways, TFs, and miRNAs have aided in the better understanding of molecular mechanisms underlying PD and its potential core target genes.

Aims It has been reported that allopregnanolone (AP alpha) promotes the neurogenesis of the neural progenitor cells (NPCs) in the subventricular zone (SVZ) and prevents the decrease of dopaminergic neurons in 6-hydroxydopamine (6-OHDA)-treated mice by binding to gamma-aminobutyric acid A receptor (GABAAR) and then opening voltage-gated L-type Ca(2+)channel, but the underlying mechanisms remain elusive. The aim of this study was to explore the possible involvement of GABAAR and calcium/calmodulin-dependent protein kinase II delta 3 (CaMKII delta 3) in this process. Methods 6-OHDA-treated mice and primary cultured midbrain cells were administrated with AP alpha and GABAAR antagonist bicuculline (Bic), and the proliferation and differentiation of NPCs, the tyrosine hydroxylase (TH)-positive neurons and their fibers, the expression levels of CaMKII delta 3 and brain-derived neurotrophic factor (BDNF), and motor functions were measured using ELISA, immunohistochemical staining, real-time RT-PCR, Western blot, and behavioral test. Results Allopregnanolone significantly promoted the phosphorylation of cytoplasmic CaMKII delta 3 and its nuclear translocation by binding to GABAAR, which, in turn, increased the expression levels of BDNF. This may account for the findings that the exogenous AP alpha enhanced the proliferation and differentiation of NPCs, and ameliorated the nigrostriatal system and behavioral performance in 6-OHDA-treated mice. Conclusions Allopregnanolone may directly activate GABAAR, which, in turn, enhance the proliferation and differentiation of NPCsviaupregulating the expression levels of CaMKII delta 3, and finally contribute to the restoration of dopaminergic neurons in 6-OHDA-treated mice.