Title:Estrogens as a Possible Therapeutic Strategy for the Management of
Neuroinflammation and Neuroprotection in COVID-19
Volume: 21
Issue: 10
Author(s): Cindy Bandala*, Noemí Cárdenas-Rodríguez, Samuel Reyes-Long, Alfredo Cortés-Algara, Itzel Jatziri Contreras-García, Teresita Rocío Cruz-Hernández, Alfonso Alfaro-Rodriguez, José Luis Cortes-Altamirano, Martín Perez-Santos, Maricruz Anaya-Ruiz and Eleazar Lara-Padilla*
Affiliation:
- Higher School of Medicine, National Polytechnic Institute, Mexico City, 11340, Mexico
- Higher School of Medicine, National Polytechnic Institute, Mexico City, 11340, Mexico
Keywords:
Estrogens, ACE2, Ang (1-7), SARS-CoV-2, COVID-19, neuroprotection, neuroinflammation.
Abstract: The Coronavirus disease 2019 (COVID-19) affects several tissues, including the central and
peripheral nervous system. It has also been related to signs and symptoms that suggest neuroinflammation
with possible effects in the short, medium, and long term. Estrogens could have a positive impact
on the management of the disease, not only due to its already known immunomodulator effect,
but also activating other pathways that may be important in the pathophysiology of COVID-19, such
as the regulation of the virus receptor and its metabolites. In addition, they can have a positive effect
on neuroinflammation secondary to pathologies other than COVID-19. The aim of this study is to analyze
the molecular mechanisms that link estrogens with their possible therapeutic effect for neuroinflammation
related to COVID-19. Advanced searches were performed in scientific databases as Pub-
Med, ProQuest, EBSCO, the Science Citation index, and clinical trials. Estrogens have been shown to
participate in the immune modulation of the response to severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2). In addition to this mechanism, we propose that estrogens can regulate the expression
and activity of the Angiotensin-converting enzyme 2 (ACE2), reestablishing its cytoprotective
function, which may be limited by its interaction with SARS-CoV-2. In this proposal, estrogens
and estrogenic compounds could increase the synthesis of Angiotensin-(1-7) (Ang-(1-7)) that acts
through the Mas receptor (MasR) in cells that are being attacked by the virus. Estrogens can be a
promising, accessible, and low-cost treatment for neuroprotection and neuroinflammation in patients
with COVID-19, due to its direct immunomodulatory capacity in decreasing cytokine storm and increasing
cytoprotective capacity of the axis ACE2/Ang (1-7)/MasR.
