Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations
Por:
Mendez-Garcia, Lucia A., Escobedo, Galileo, Gerardo Minguer-Uribe, Alan, Viurcos-Sanabria, Rebeca, Aguayo-Guerrero, Jose A., Damian Carrillo-Ruiz, Jose, Solleiro-Villavicencio, Helena
Publicada:
16 sep 2022
Categoría:
Cellular and molecular neuroscience
Resumen:
SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This
virus can infect various cells and tissues, including the brain, for
which numerous neurological symptoms have been reported, ranging from
mild and non-life-threatening (e.g., headaches, anosmia, dysgeusia, and
disorientation) to severe and life-threatening symptoms (e.g.,
meningitis, ischemic stroke, and cerebral thrombosis). The cellular
receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), an
enzyme that belongs to the renin-angiotensin system (RAS). RAS is an
endocrine system that has been classically associated with regulating
blood pressure and fluid and electrolyte balance; however, it is also
involved in promoting inflammation, proliferation, fibrogenesis, and
lipogenesis. Two pathways constitute the RAS with counter-balancing
effects, which is the key to its regulation. The first axis (classical)
is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang)
II, and angiotensin type 1 receptor (AT1R) as the main effector, which
-when activated- increases the production of aldosterone and
antidiuretic hormone, sympathetic nervous system tone, blood pressure,
vasoconstriction, fibrosis, inflammation, and reactive oxygen species
(ROS) production. Both systemic and local classical RAS' within the
brain are associated with cognitive impairment, cell death, and
inflammation. The second axis (non-classical or alternative) includes
ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that
activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions.
Thus, the alternative RAS axis enhances cognition, synaptic remodeling,
cell survival, cell signal transmission, and
antioxidant/anti-inflammatory mechanisms in the brain. In a
physiological state, both RAS axes remain balanced. However, some
factors can dysregulate systemic and local RAS arms. The binding of
SARS-CoV-2 to ACE2 causes the internalization and degradation of this
enzyme, reducing its activity, and disrupting the balance of systemic
and local RAS, which partially explain the appearance of some of the
neurological symptoms associated with COVID-19. Therefore, this review
aims to analyze the role of RAS in the development of the neurological
effects due to SARS-CoV-2 infection. Moreover, we will discuss the
RAS-molecular targets that could be used for therapeutic purposes to
treat the short and long-term neurological COVID-19-related sequelae.
Filiaciones:
Gen Hosp Mexico Dr Eduardo Liceaga, Res Div, Lab Immunometab, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Cellular Physiol Inst, Lab Mol Neuropathol, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Sch Med, PECEM, Mexico City, DF, Mexico
Gen Hosp MexicoDr Eduardo Liceaga, Res Directorate, Mexico City, DF, Mexico
Gen Hosp Mexico Dr Eduardo Liceaga, Dept Neurol & Neurosurg, Mexico City, DF, Mexico
Univ Anahuac, Fac Ciencias Salud, Huixquilucan, Mexico
Univ Autonoma Ciudad Mexico, Ciencias Genom, Mexico City, DF, Mexico
Green Published, gold, All Open Access, Gold, Green
|