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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo de Revisão
• Fonte: MOLECULAR PSYCHIATRY; v. 26, n. 4 DEC 2020.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 18/17504-5 - Efeitos comportamentais e moleculares da modulação farmacológica dos receptores P2Y2 em modelo animal da Doença de Alzheimer
• Beneficiário: Deidiane Elisa Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/24553-5 - O papel do receptor P2Y1 na Doença de Parkinson
• Beneficiário: Roberta Andrejew Caetano
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/19128-2 - Mecanismos de metástase de tumores infantis para a medula óssea
• Beneficiário: Claudiana Lameu
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/13345-1 - Doença de Huntington: envolvimento de Huntingtin no controle do comprometimento celular
• Beneficiário: Talita Glaser
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/26852-0 - Estudo do antagonismo de receptores purinérgicos no processo inflamatório e ativação microglial em modelos in vivo e in vitro de Doença de Parkinson
• Beneficiário: Ágatha Oliveira Giacomelli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/07366-4 - Receptores de purinas e cininas como alvos de estudo e intervenção terapêutica em doenças neurológicas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático