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

Author(s)

Ribeiro, Deidiane Elisa ^[1] ; Oliveira-Giacomelli, Agatha ^[1] ; Glaser, Talita ^[1] ; Arnaud-Sampaio, Vanessa F. ^[1] ; Andrejew, Roberta ^[1] ; Dieckmann, Luiz ^[2] ; Baranova, Juliana ^[1] ; Lameu, Claudiana ^[1] ; Ratajczak, Mariusz Z. ^[3] ; Ulrich, Henning ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo - Brazil

^[3] Univ Louisville, Dept Med, Stem Cell Program, Louisville, KY 40292 - USA

• Document type: Review article
• Source: MOLECULAR PSYCHIATRY; v. 26, n. 4 DEC 2020.
• Web of Science Citations: 2

Abstract

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. (AU)

• FAPESP's process: 18/17504-5 - Behavioral and molecular effects of pharmacological modulation of the P2Y2 receptors in an animal model of Alzheimer's Disease
• Grantee: Deidiane Elisa Ribeiro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/24553-5 - The role of P2Y1 receptor in Parkinsons Disease
• Grantee: Roberta Andrejew Caetano
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/19128-2 - Metastasis mechanisms of childhood tumors to bone marrow
• Grantee: Claudiana Lameu
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/13345-1 - Huntington's disease: Huntingtin roles during cell fate decision
• Grantee: Talita Glaser
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/26852-0 - Study of purinergic receptors antagonism in the inflammatory process and microglial cells activation using in vitro and in vivo models of Parkinsons Disease
• Grantee: Ágatha Oliveira Giacomelli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants