ACE2 Receptor and TMPRSS2 Protein Expression Patterns in the Human Brainstem Reveal Anatomical Regions Potentially Vulnerable to SARS-CoV-2 Infection.
Aron EmmiAleksandar TushevskiAlessandro SinigagliaSilvia BarbonMichele SandreElena StoccoVeronica MacchiAngelo AntoniniLuisa BarzonAndrea PorzionatoRaffaele De CaroPublished in: ACS chemical neuroscience (2023)
Angiotensin-converting enzyme 2 receptor (ACE2R) is a transmembrane protein expressed in various tissues throughout the body that plays a key role in the regulation of blood pressure. Recently, ACE2R has gained significant attention due to its involvement in the pathogenesis of COVID-19, the disease caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). While ACE2 receptors serve as entry points for the novel coronavirus, Transmembrane Serine Protease 2 (TMPRSS2), an enzyme located on the cell membrane, is required for SARS-CoV-2 S protein priming. Even though numerous studies have assessed the effects of COVID-19 on the brain, very little information is available concerning the distribution of ACE2R and TMPRSS2 in the human brain, with particular regard to their topographical expression in the brainstem. In this study, we investigated the expression of ACE2R and TMPRSS2 in the brainstem of 18 adult subjects who died due to pneumonia/respiratory insufficiency. Our findings indicate that ACE2R and TMPRSS2 are expressed in neuronal and glial cells of the brainstem, particularly at the level of the vagal nuclei of the medulla and the midbrain tegmentum, thus confirming the expression and anatomical localization of these proteins within specific human brainstem nuclei. Furthermore, our findings help to define anatomically susceptible regions to SARS-CoV-2 infection in the brainstem, advancing knowledge on the neuropathological underpinnings of neurological manifestations in COVID-19.
Keyphrases
- angiotensin converting enzyme
- sars cov
- respiratory syndrome coronavirus
- angiotensin ii
- coronavirus disease
- poor prognosis
- binding protein
- blood pressure
- endothelial cells
- gene expression
- cell proliferation
- cerebral ischemia
- adipose tissue
- resting state
- oxidative stress
- single cell
- skeletal muscle
- long non coding rna
- functional connectivity
- single molecule
- amino acid
- multiple sclerosis
- neuropathic pain
- intensive care unit