Role of microglia adenosine A(2A) receptors in retinal and brain neurodegenerative diseases.

Ana R Santiago,Filipa I Baptista,Gonçalo Cristóvão,Paulo F Santos,Catarina A Gomes,António F Ambrósio,Rodrigo A Cunha

doi:10.1155/2014/465694

Abstract

Neuroinflammation mediated by microglial cells in the brain has been commonly associated with neurodegenerative diseases. Whether this microglia-mediated neuroinflammation is cause or consequence of neurodegeneration is still a matter of controversy. However, it is unequivocal that chronic neuroinflammation plays a role in disease progression and halting that process represents a potential therapeutic strategy. The neuromodulator adenosine emerges as a promising targeting candidate based on its ability to regulate microglial proliferation, chemotaxis, and reactivity through the activation of its G protein coupled A2A receptor (A2AR). This is in striking agreement with the ability of A2AR blockade to control several brain diseases. Retinal degenerative diseases have been also associated with microglia-mediated neuroinflammation, but the role of A2AR has been scarcely explored. This review aims to compare inflammatory features of Parkinson's and Alzheimer's diseases with glaucoma and diabetic retinopathy, discussing the therapeutic potential of A2AR in these degenerative conditions.

Highlights

IntroductionMediators of Inflammation and coworkers [9] in the visual system: light deprivation and the subsequent decrease in the workload of neuronal circuits involved in visual processing lead to the engulfment of synaptic elements by microglia
In the central nervous system (CNS), microglial cells participate in innate immunity; microglia can respond to different types of signals, namely the presence of pathogens or to intrinsic signals, namely diffusible mediators released by stressed neurons, astrocytes or microglia
The present review mainly focuses on the contribution of microglia to the pathophysiology of neurodegeneration in the brain and the retina, any attempt to interfere with microglia in pathological conditions needs to take into account the role of microglia in physiological conditions

Summary

Introduction

Mediators of Inflammation and coworkers [9] in the visual system: light deprivation and the subsequent decrease in the workload of neuronal circuits involved in visual processing lead to the engulfment of synaptic elements by microglia This physiological process, termed synaptic pruning, is regulated by the immune system; synapses and axons to be phagocytosed are labeled by the complement components C1q and C3, which prompt their selective recognition by microglial cells [10,11,12]. In addition to their role in synaptic pruning, microglia regulate synapse formation [20,21,22] This function has been shown to be dependent on the production and release of mediators, such as brain-derived neurotrophic factor [20] or interleukin- (IL-) 10 [22], other diffusible mediators are likely to be involved.

Phagocytosis

Findings

Concluding Remarks