Understanding the Role of Adenosine A2AR Heteroreceptor Complexes in Neurodegeneration and Neuroinflammation

Frontiers in Neuroscience
Dasiel O Borroto-EscuelaKjell Fuxe

Abstract

Adenosine is a nucleoside mainly formed by degradation of ATP, located intracellularly or extracellularly, and acts as a neuromodulator. It operates as a volume transmission signal through diffusion and flow in the extracellular space to modulate the activity of both glial cells and neurons. The effects of adenosine are mediated via four adenosine receptor subtypes: A1R, A2AR, A2BR, A3R. The A2AR has a wide-spread distribution but it is especially enriched in the ventral and dorsal striatum where it is mainly located in the striato-pallidal GABA neurons at a synaptic and extrasynaptic location. A number of A2AR heteroreceptor complexes exist in the striatum. The existence of A2AR-D2R heteroreceptor complexes with antagonistic A2AR-D2R interactions in the striato-pallidal GABA neurons is well-known with A2AR activation inhibiting Gi/o mediated signaling of D2Rs. A2AR-mGluR5 heteroreceptor complexes were also found in with synergistic receptor-receptor interactions enhancing the inhibition of the D2R protomer signaling. They are located mainly in extrasynaptic regions of the striato-pallidal GABA neurons. Results recently demonstrated the existence of brain A2AR-A2BR heteroreceptor complexes, in which A2BR protomer constitutively...Continue Reading

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Citations

Jan 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alexei A SurguchevAndrei Surguchov
Jun 5, 2020·Cells·Karolina WydraMałgorzata Filip
Jan 15, 2019·Journal of Neural Transmission·Dasiel O Borroto-Escuela, Kjell Fuxe
Nov 3, 2020·Frontiers in Cellular and Infection Microbiology·Caitlin TiceDianne Langford
Feb 27, 2021·Molecular Medicine·Theodora NtetsikaIoanna Markaki

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Methods Mentioned

BETA
PCR
confocal microscopy
proximity
co-immunoprecipitation
proximity ligation assay

Software Mentioned

PLA

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