scholarly journals Analysis of master transcription factors related to Parkinson’s disease through the gene transcription regulatory network

2019 ◽  
Author(s):  
Li Wei ◽  
Fei He ◽  
Wen Zhang ◽  
Wenhua Chen ◽  
Bo Yu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Gene Transcription ◽  
Regulatory Network ◽  
Transcription Regulatory Network

scholarly journals Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110097
Author(s):  
Kui Cui ◽  
Fan Yang ◽  
Turan Tufan ◽  
Muhammad U. Raza ◽  
Yanqiang Zhan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Disease Model ◽  
Neuronal Loss ◽  
Mrna Levels ◽  
Gene Therapies ◽  
Protein Levels ◽  
Dopaminergic Systems ◽  
And Function

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

The Effect of Dopamine on Gene Expression of Alpha-synuclein and Transcription Factors GATA-1, GATA-2, and ZSCAN21 in Parkinson’s Disease

2018 ◽  
Vol 12 (5) ◽  
pp. 410-418
Author(s):  
A. K. Emelyanov ◽  
A. O. Lavrinova ◽  
E. M. Litusova ◽  
N. A. Knyazev ◽  
D. G. Kulabukhova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Alpha Synuclein

Mutational screening of the Mitochondrial transcription factors B1 and B2 (TFB1M and TFB2M) in Parkinson's disease

2009 ◽  
Vol 15 (6) ◽  
pp. 468-470 ◽  
Author(s):  
Elena Sánchez-Ferrero ◽  
Eliecer Coto ◽  
Marta Blázquez ◽  
René Ribacoba ◽  
Luis M. Guisasola ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Mitochondrial Transcription ◽  
Mutational Screening

scholarly journals Transcriptional Factor NF-κB as a Target for Therapy in Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Patrick M. Flood ◽  
Li Qian ◽  
Lynda J. Peterson ◽  
Feng Zhang ◽  
Jing-Shan Shi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Inflammatory Mediator ◽  
Transcriptional Factor ◽  
Classical Pathway ◽  
Nuclear Factor ◽  
Inflammatory Conditions ◽  
Inflammatory Mediator Production ◽  
Ikk Complex

Parkinson's disease (PD) is a neurodegenerative condition characterized by chronic inflammation. Nuclear factorκB (NF-κB) is a family of inducible transcription factors that are expressed in a wide variety of cells and tissues, including microglia, astrocytes, and neurons, and the classical NF-κB pathway plays a key role in the activation and regulation of inflammatory mediator production during inflammation. Activation of the classical NF-κB pathway is mediated through the activity of the IKK kinase complex, which consists of a heterotrimer of IKKα, IKKβ, and IKKγsubunits. Targeting NF-κB has been proposed as an approach to the treatment of acute and chronic inflammatory conditions, and the use of inhibitors specific for either IKKβor IKKγhas now been found to inhibit neurodegeneration of TH+ DA-producing neurons in murine and primate models of Parkinson's disease. These studies suggest that targeting the classical pathway of NF-κB through the inhibition of the IKK complex can serve as a useful therapeutic approach to the treatment of PD.

scholarly journals Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease

2021 ◽  
Author(s):  
Xi Yin ◽  
Miao Wang ◽  
Wei Wang ◽  
Tong Chen ◽  
Ge Song ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Regulatory Network ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Rab Protein ◽  
Healthy Donors ◽  
Geo Database

Abstract Parkinson’s disease (PD) is a common neurodegenerative disease and the mechanism underlying PD pathogenesis is incompletely understood. Increasing evidence indicates that microRNA (miRNA) plays critical regulatory role in the pathogenesis of PD. This study aimed to determine the miRNA-mRNA regulatory network for PD. The differentially expressed miRNAs (DEmis) and genes (DEGs) between PD patients and healthy donors were screened from miRNA dataset GSE16658 and mRNA dataset GSE100054 downloaded from the Gene Expression Omnibus (GEO) database. Target genes of the DEmis were selected when predicted by 3 or 4 online databases and overlapped with DEGs from GSE100054. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Metascape analytic tool. The correlation between the screened genes and PD was evaluated by the online tool Comparative Toxicogenomics Database (CTD). The protein-protein interactions (PPI) network was built by STRING platform. Finally, we testify the expression of members of the miRNA-mRNA regulatory network in the blood samples collected from PD patients and healthy donors by using qRT-PCR. 1505 upregulated and 1302 downregulated DEGs, 77 upregulated DEmis and 112 downregulated DEmis were preliminarily screened from GEO database. Through further functional enrichment analysis, 10 PD-related hub genes were selected, including RAC1, IRS2, LEPR, PPARGC1A, CAMKK2, RAB10, RAB13, RAB27B, RAB11A and JAK2, which were mainly involved in Rab protein signaling transduction, AMPK signaling pathway and signaling by Leptin. The miRNA-mRNA regulatory network was constructed with 10 hub genes and their interacting miRNAs overlapped with DEmis, including miR-30e-5p, miR-142-3p, miR-101-3p, miR-32-3p, miR-508-5p, miR-642a-5p, miR-19a-3p and miR-21-5p. Analysis on clinical samples verified significant upregulation of LEPR and downregulation of miR-101-3p in PD patients compared with healthy donors. In the study, the potential miRNA-mRNA regulatory network was constructed in PD, which may provide novel insight into pathogenesis and treatment of PD.

scholarly journals Reconstructing the maize leaf regulatory network using ChIP-seq data of 104 transcription factors

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoyu Tu ◽  
María Katherine Mejía-Guerra ◽  
Jose A. Valdes Franco ◽  
David Tzeng ◽  
Po-Yu Chu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Network ◽  
Large Scale ◽  
Eukaryotic Cell ◽  
Core Network ◽  
Binding Studies ◽  
Evolutionary Trajectory ◽  
Maize Leaf ◽  
Scale Free ◽  
Transcription Regulatory Network

Abstract The transcription regulatory network inside a eukaryotic cell is defined by the combinatorial actions of transcription factors (TFs). However, TF binding studies in plants are too few in number to produce a general picture of this complex network. In this study, we use large-scale ChIP-seq to reconstruct it in the maize leaf, and train machine-learning models to predict TF binding and co-localization. The resulting network covers 77% of the expressed genes, and shows a scale-free topology and functional modularity like a real-world network. TF binding sequence preferences are conserved within family, while co-binding could be key for their binding specificity. Cross-species comparison shows that core network nodes at the top of the transmission of information being more conserved than those at the bottom. This study reveals the complex and redundant nature of the plant transcription regulatory network, and sheds light on its architecture, organizing principle and evolutionary trajectory.

scholarly journals Targeting Nrf2-Mediated Gene Transcription by Extremely Potent Synthetic Triterpenoids Attenuate Dopaminergic Neurotoxicity in the MPTP Mouse Model of Parkinson's Disease

2013 ◽  
Vol 18 (2) ◽  
pp. 139-157 ◽  
Author(s):  
Navneet Ammal Kaidery ◽  
Rebecca Banerjee ◽  
Lichuan Yang ◽  
Natalya A. Smirnova ◽  
Dmitry M. Hushpulian ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Gene Transcription

Role of neuroinflammation and latent transcription factors in pathogenesis of Parkinson’s disease

2016 ◽  
Vol 38 (12) ◽  
pp. 1111-1122 ◽  
Author(s):  
Rishi Pal ◽  
Prafulla Chandra Tiwari ◽  
Rajendra Nath ◽  
Kamlesh Kumar Pant
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors

scholarly journals Homogenous generation of dopaminergic neurons from multiple hiPSC lines by transient expression of transcription factors

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Sameehan Mahajani ◽  
Anupam Raina ◽  
Claudia Fokken ◽  
Sebastian Kügler ◽  
Mathias Bähr
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Transient Expression ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Variable Yield ◽  
Experimental Systems ◽  
Induced Pluripotent ◽  
Transcription Factor Expression

AbstractA major hallmark of Parkinson's disease is loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The pathophysiological mechanisms causing this relatively selective neurodegeneration are poorly understood, and thus experimental systems allowing to study dopaminergic neuron dysfunction are needed. Induced pluripotent stem cells (iPSCs) differentiated toward a dopaminergic neuronal phenotype offer a valuable source to generate human dopaminergic neurons. However, currently available protocols result in a highly variable yield of dopaminergic neurons depending on the source of hiPSCs. We have now developed a protocol based on HBA promoter-driven transient expression of transcription factors by means of adeno-associated viral (AAV) vectors, that allowed to generate very consistent numbers of dopaminergic neurons from four different human iPSC lines. We also demonstrate that AAV vectors expressing reporter genes from a neuron-specific hSyn1 promoter can serve as surrogate markers for maturation of hiPSC-derived dopaminergic neurons. Dopaminergic neurons differentiated by transcription factor expression showed aggravated neurodegeneration through α-synuclein overexpression, but were not sensitive to γ-synuclein overexpression, suggesting that these neurons are well suited to study neurodegeneration in the context of Parkinson’s disease.

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