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Gene Regulation in Activated Microglia by Adenosine A Receptor Agonists: a Transcriptomics Study

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Publisher Springer
Date 2023 Jan 26
PMID 36703008
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Abstract

Most neurodegenerative disorders, including the two most common, Alzheimer's disease (AD) and Parkinson's disease (AD), course with activation of microglia, the resident innate immune cells of the central nervous system. A adenosine receptor (AR) agonists have been proposed to be neuroprotective by regulating the phenotype of activated microglia. RNAseq was performed using samples isolated from lipopolysaccharide/interferon-γ activated microglia treated with 2-Cl-IB-MECA, a selective AR agonist. The results showed that the number of negatively regulated genes in the presence of 2-Cl-IB-MECA was greater than the number of positively regulated genes. Gene ontology enrichment analysis showed regulation of genes participating in several cell processes, including those involved in immune-related events. Analysis of known and predicted protein-protein interactions showed that Smad3 and Sp1 are transcription factors whose genes are regulated by AR activation. Under the conditions of cell activation and agonist treatment regimen, 2-Cl-IB-MECA did not lead to any tendency to favor the expression of genes related to neuroprotective microglia (M2).

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References
1.
Joshi A, Minhas P, Liddelow S, Haileselassie B, Andreasson K, Dorn 2nd G . Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration. Nat Neurosci. 2019; 22(10):1635-1648. PMC: 6764589. DOI: 10.1038/s41593-019-0486-0. View

2.
Lee J, Jhun B, Oh Y, Lee J, Choe W, Baik H . Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Neurosci Lett. 2005; 396(1):1-6. DOI: 10.1016/j.neulet.2005.11.004. View

3.
Ramirez A, de Hoz R, Salobrar-Garcia E, Salazar J, Rojas B, Ajoy D . The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma. Front Aging Neurosci. 2017; 9:214. PMC: 5498525. DOI: 10.3389/fnagi.2017.00214. View

4.
Yan L, Burbiel J, Maass A, Muller C . Adenosine receptor agonists: from basic medicinal chemistry to clinical development. Expert Opin Emerg Drugs. 2003; 8(2):537-76. DOI: 10.1517/14728214.8.2.537. View

5.
Galvao J, Elvas F, Martins T, Cordeiro M, Ambrosio A, Santiago A . Adenosine A3 receptor activation is neuroprotective against retinal neurodegeneration. Exp Eye Res. 2015; 140:65-74. DOI: 10.1016/j.exer.2015.08.009. View