Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology.

Deidiane Elisa Ribeiro, Ágatha Oliveira-Giacomelli, Talita Glaser, Vanessa F Arnaud-Sampaio, Roberta Andrejew, Luiz Dieckmann, Juliana Baranova, Claudiana Lameu, Mariusz Z Ratajczak, Henning Ulrich

Molecular psychiatry 2021 Apr

filter terms:

Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called "cytokine storm". Both pro-inflammatory factors and viruses may cross the blood-brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson's and Alzheimer's disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.

Citation

Deidiane Elisa Ribeiro, Ágatha Oliveira-Giacomelli, Talita Glaser, Vanessa F Arnaud-Sampaio, Roberta Andrejew, Luiz Dieckmann, Juliana Baranova, Claudiana Lameu, Mariusz Z Ratajczak, Henning Ulrich. Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology. Molecular psychiatry. 2021 Apr;26(4):1044-1059