The roles of Eph receptors, neuropilin-1, P2X7, and CD147 in COVID-19-associated neurodegenerative diseases: inflammasome and JaK inhibitors as potential promising therapies

Cell Mol Biol Lett. 2022 Feb 2;27(1):10. doi: 10.1186/s11658-022-00311-1.

Abstract

The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.

Keywords: Alzheimer’s disease; CD147; CNS; COVID-19; Cytokine; Ephrin; Inflammasome; Jak; Neurodegenerative diseases; Neuropilin-1; P2X7; Parkinson’s disease.

Publication types

  • Letter
  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antiviral Agents / therapeutic use
  • Basigin / genetics
  • Basigin / metabolism
  • COVID-19 / genetics
  • COVID-19 / metabolism
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Central Nervous System / virology
  • Ephrins / genetics
  • Ephrins / metabolism
  • Gene Expression Regulation
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / genetics
  • Humans
  • Immunologic Factors / therapeutic use
  • Inflammasomes / drug effects*
  • Inflammasomes / genetics
  • Inflammasomes / metabolism
  • Janus Kinase Inhibitors / therapeutic use
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / genetics
  • Janus Kinases / metabolism
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / virology
  • Neuropilin-1 / genetics
  • Neuropilin-1 / metabolism
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / metabolism
  • Receptors, Virus / antagonists & inhibitors
  • Receptors, Virus / genetics*
  • Receptors, Virus / metabolism
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / pathogenicity
  • Signal Transduction
  • Virus Internalization / drug effects*

Substances

  • Antiviral Agents
  • BSG protein, human
  • Ephrins
  • Immunologic Factors
  • Inflammasomes
  • Janus Kinase Inhibitors
  • NRP1 protein, human
  • P2RX7 protein, human
  • Receptors, Purinergic P2X7
  • Receptors, Virus
  • Basigin
  • Neuropilin-1
  • Janus Kinases
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2