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Review
. 2022 Feb 2;27(1):10.
doi: 10.1186/s11658-022-00311-1.

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

Hamidreza Zalpoor #  1   2   3 , Abdullatif Akbari #  4 , Azam Samei  5 , Razieh Forghaniesfidvajani  4 , Monireh Kamali  6 , Azadeh Afzalnia  6 , Shirin Manshouri  6 , Fatemeh Heidari  7 , Majid Pornour  8 , Majid Khoshmirsafa  9 , Hossein Aazami  10 , Farhad Seif  11   12
Affiliations
Review

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

Hamidreza Zalpoor et al. Cell Mol Biol Lett. .

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.

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Conflict of interest statement

The authors of this study declare no competing interest.

Figures

Fig. 1
Fig. 1
ACE2, Eph receptors and ephrin ligands, neuropilin-1 (NRP-1), transmembrane serine protease 2 (TMPRSS2), P2X7, and CD147 are shown as entry receptors for SARS-CoV-2 in neurodegenerative diseases. ACE2, EphA/B receptors, and IL-6 receptor use JaK2/STAT3 for signal transduction; thus they may be targeted by JaK inhibitors (JaKinibs). Moreover, ACE2, EphA/B receptors, TMPRSS2, (NRP-1), P2X7, and CD147 can activate NLRP3 inflammasome to secrete IL-1β and IL-18; therefore, they may be targeted by inflammasome inhibitors or IL-1β and IL-18 monoclonal antibodies or antagonists
See this image and copyright information in PMC

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