Preprint Review Version 1 This version is not peer-reviewed

Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS

Version 1 : Received: 17 March 2020 / Approved: 18 March 2020 / Online: 18 March 2020 (16:52:28 CET)

A peer-reviewed article of this Preprint also exists.

Illes, P.; Rubini, P.; Ulrich, H.; Zhao, Y.; Tang, Y. Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS. Cells 2020, 9, 1108. Illes, P.; Rubini, P.; Ulrich, H.; Zhao, Y.; Tang, Y. Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS. Cells 2020, 9, 1108.

Journal reference: Cells 2020, 9, 1108
DOI: 10.3390/cells9051108

Abstract

Microglial cells, the resident macrophages of the CNS, exist in a process-bearing, ramified/surveying phenotype under resting conditions. Upon activation by cell damaging factors they get transformed to an amoeboid phenotype releasing various cell products including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen/nitrogen species and the excytotoxic ATP and glutamate. In addition, they engulf pathogenic bacteria or cell debris and phagocytose them. However, already resting/surveying microglia has a number of important physiological functions in the CNS; they e.g. shield small disruptions of the blood-brain barrier by their processes, dynamically interact with synaptic structures and clear surplus synapses during development. In neurodegenerative illnesses they aggravate the original disease by a microglia-based compulsory neuroinflammatory reaction. Therefore, the blockade of this reaction improves the outcome of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. The function of microglia is regulated by a whole array of purinergic receptors classified as P2Y12, P2Y6, P2Y4, P2X4, P2X7, A2A, A3, and being targets for endogenous ATP, ADP, or adenosine. ATP is sequentially degraded by the ecto-nucleotidases and 5’-nucleotidase enzymes to the weak adenosine agonist inosine as an end-product. The appropriate selective agonists/antagonists for purinergic receptors as well as the respective enzyme inhibitors may profoundly interfere with microglial functions and reconstitute the homeostasis of the CNS disturbed by neuroinflammation.

Subject Areas

surveying microglia; amoeboid microglia; P2X receptors; P2Y receptors; P1 receptors; CD39; CD73; microglia-neuron cross talk; phagocytosis; microglial products; neuroinflammation

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