scholarly journals The Possible Role of Microbial Proteases in Facilitating SARS-CoV-2 Brain Invasion

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 966
Author(s):  
Nozethu Mjokane ◽  
Olufemi S. Folorunso ◽  
Adepemi O. Ogundeji ◽  
Olihile M. Sebolai
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Brain Endothelial Cells ◽  
Limited Information ◽  
Brain Invasion ◽  
Invasion Mechanism ◽  
Intervention Measures ◽  
The Brain

SARS-CoV-2 has been shown to display proclivity towards organs bearing angiotensin-converting enzyme (ACE2) expression cells. Of interest herein is the ability of the virus to exhibit neurotropism. However, there is limited information on how this virus invades the brain. With this contribution, we explore how, in the context of a microbial co-infection using a cryptococcal co-infection as a model, SARS-CoV-2 could reach the brain. We theorise that the secretion of proteases by disseminated fungal cells might also activate the S2 domain of the viral spike glycoprotein for membrane fusion with brain endothelial cells leading to endocytosis. Understanding this potential invasion mechanism could lead to better SARS-CoV-2 intervention measures, which may also be applicable in instances of co-infection, especially with protease-secreting pathogens.

scholarly journals The Role of BAR Proteins and the Glycocalyx in Brain Endothelium Transcytosis

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2685
Author(s):  
Diana M. Leite ◽  
Diana Matias ◽  
Giuseppe Battaglia
Keyword(s):  
Endothelial Cells ◽  
Small Molecules ◽  
The Other ◽  
Brain Endothelial Cells ◽  
Brain Endothelium ◽  
Transcellular Transport ◽  
Molecular Transporters ◽  
Membrane Bound ◽  
The Brain

Within the brain, endothelial cells lining the blood vessels meticulously coordinate the transport of nutrients, energy metabolites and other macromolecules essential in maintaining an appropriate activity of the brain. While small molecules are pumped across specialised molecular transporters, large macromolecular cargos are shuttled from one side to the other through membrane-bound carriers formed by endocytosis on one side, trafficked to the other side and released by exocytosis. Such a process is collectively known as transcytosis. The brain endothelium is recognised to possess an intricate vesicular endosomal network that mediates the transcellular transport of cargos from blood-to-brain and brain-to-blood. However, mounting evidence suggests that brain endothelial cells (BECs) employ a more direct route via tubular carriers for a fast and efficient transport from the blood to the brain. Here, we compile the mechanism of transcytosis in BECs, in which we highlight intracellular trafficking mediated by tubulation, and emphasise the possible role in transcytosis of the Bin/Amphiphysin/Rvs (BAR) proteins and glycocalyx (GC)—a layer of sugars covering BECs, in transcytosis. Both BAR proteins and the GC are intrinsically associated with cell membranes and involved in the modulation and shaping of these membranes. Hence, we aim to summarise the machinery involved in transcytosis in BECs and highlight an uncovered role of BAR proteins and the GC at the brain endothelium.

Role of angiotensin-converting enzyme 2 (ACE2) in diabetic cardiovascular complications

2013 ◽  
Vol 126 (7) ◽  
pp. 471-482 ◽  
Author(s):  
Vaibhav B. Patel ◽  
Nirmal Parajuli ◽  
Gavin Y. Oudit
Keyword(s):  
Diabetes Mellitus ◽  
Angiotensin Converting Enzyme ◽  
Vascular Function ◽  
Systolic Dysfunction ◽  
Cardiovascular Complications ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Obesity And Diabetes

Diabetes mellitus results in severe cardiovascular complications, and heart disease and failure remain the major causes of death in patients with diabetes. Given the increasing global tide of obesity and diabetes, the clinical burden of diabetes-induced cardiovascular disease is reaching epidemic proportions. Therefore urgent actions are needed to stem the tide of diabetes which entails new prevention and treatment tools. Clinical and pharmacological studies have demonstrated that AngII (angiotensin II), the major effector peptide of the RAS (renin–angiotensin system), is a critical promoter of insulin resistance and diabetes mellitus. The role of RAS and AngII has been implicated in the progression of diabetic cardiovascular complications and AT1R (AngII type 1 receptor) blockers and ACE (angiotensin-converting enzyme) inhibitors have shown clinical benefits. ACE2, the recently discovered homologue of ACE, is a monocarboxypeptidase which converts AngII into Ang-(1–7) [angiotensin-(1–7)] which, by virtue of its actions on the MasR (Mas receptor), opposes the effects of AngII. In animal models of diabetes, an early increase in ACE2 expression and activity occurs, whereas ACE2 mRNA and protein levels have been found to decrease in older STZ (streptozotocin)-induced diabetic rats. Using the Akita mouse model of Type 1 diabetes, we have recently shown that loss of ACE2 disrupts the balance of the RAS in a diabetic state and leads to AngII/AT1R-dependent systolic dysfunction and impaired vascular function. In the present review, we will discuss the role of the RAS in the pathophysiology and treatment of diabetes and its complications with particular emphasis on potential benefits of the ACE2/Ang-(1–7)/MasR axis activation.

Sign in / Sign up

Export Citation Format

Share Document