10-22-2021, 12:10 PM
https://www.nature.com/articles/s41593-021-00926-1
Covid naśladuje chorobę genetyczną powodującą wylewy. Ale dalej skupiajmy się tylko na śmierciach i nazywajmy każdego kto nie umarł wyzdrowiałym.
Our data suggest that, in COVID-19, brain endothelial cells are at disproportionate risk when being infected by SARS-CoV-2 because of their dependence on NEMO activity for survival.
Cleavage of NEMO by Mpro mimics the genetic disease incontinentia pigmenti that is caused by inactivating mutations in the NEMO (IKBKG) gene. In the latter condition, patients suffer from a mix of neurological symptoms, such as encephalopathy, stroke and seizures that resemble neurological manifestations of COVID-19 (ref. 56). The absence of NEMO in mice induced a loss of endothelial cells and microvascular pathology. Subsequently, patchy hypoxia developed in the brain and the BBB became leaky. In parenchymal cells, a prominent upregulation of GFAP indicated the activation of astrocytes, in line with the finding that GFAP concentrations are elevated in the blood of patients with COVID-19 (ref. 57). An increased BBB permeability and astrocyte activation may cause epileptic seizures in patients with COVID-19 as in incontinentia pigmenti56,58.
Mpro-mediated damage of brain endothelial cells suggests that inhibitors of Mpro may prevent neurological complications of the SARS-CoV-2 infection26. Another therapeutic approach may arise from the observation that deletion of Ripk3 or inhibition of RIPK1 profoundly improved the microvascular pathology. RIPK1 inhibitors are available and have already entered clinical testing40,42 suggesting potential therapeutic options for COVID-19 as well as for incontinentia pigmenti.
Covid naśladuje chorobę genetyczną powodującą wylewy. Ale dalej skupiajmy się tylko na śmierciach i nazywajmy każdego kto nie umarł wyzdrowiałym.
Our data suggest that, in COVID-19, brain endothelial cells are at disproportionate risk when being infected by SARS-CoV-2 because of their dependence on NEMO activity for survival.
Cleavage of NEMO by Mpro mimics the genetic disease incontinentia pigmenti that is caused by inactivating mutations in the NEMO (IKBKG) gene. In the latter condition, patients suffer from a mix of neurological symptoms, such as encephalopathy, stroke and seizures that resemble neurological manifestations of COVID-19 (ref. 56). The absence of NEMO in mice induced a loss of endothelial cells and microvascular pathology. Subsequently, patchy hypoxia developed in the brain and the BBB became leaky. In parenchymal cells, a prominent upregulation of GFAP indicated the activation of astrocytes, in line with the finding that GFAP concentrations are elevated in the blood of patients with COVID-19 (ref. 57). An increased BBB permeability and astrocyte activation may cause epileptic seizures in patients with COVID-19 as in incontinentia pigmenti56,58.
Mpro-mediated damage of brain endothelial cells suggests that inhibitors of Mpro may prevent neurological complications of the SARS-CoV-2 infection26. Another therapeutic approach may arise from the observation that deletion of Ripk3 or inhibition of RIPK1 profoundly improved the microvascular pathology. RIPK1 inhibitors are available and have already entered clinical testing40,42 suggesting potential therapeutic options for COVID-19 as well as for incontinentia pigmenti.