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torsdag 4 augusti 2022

Miksi Sars-2 koronavirus voi olla hyvin tuhoisa?

Tämä artikkeli on lokakuulta 2020 ja hahmottelee  sars-2 viruksen otetta ihmisen puolustusjärjestelmään. Tämäntapainen tietämys  auttoi lopulta  terapiastrategioiden luomisessa ja mortaliteetin vähentämisessä:

. 2020 Oct 9;5(1):235.
doi: 10.1038/s41392-020-00334-0.
SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation
Free PMC article  Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to respiratory illness and multi-organ failure (MOF)  in critically ill patients. Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019 (COVID-19) clinical manifestations, the underlying mechanisms of virus-triggered inflammatory responses are currently  (2020) unknown. Here we report that SARS-CoV-2 infection activates caspase-8  ( extrinsic pathway of apoptosis) to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells. The processed inflammatory cytokines are released through the virus-induced necroptosis pathway. Virus-induced apoptosis, necroptosis, and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying SARS-CoV-2 pathogenesis. Furthermore, analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration, necrotic cell debris, and pulmonary interstitial fibrosis, typical of immune pathogenesis in the lung. The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients. These discoveries might assist the development of therapeutic strategies to treat COVID-19.

 RIPK, receptor interacting protein 1 ja 3.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=RIPK1&keywords=MLKL

 https://www.genecards.org/cgi-bin/carddisp.pl?gene=RIPK3&keywords=MLKL

 MLKL Mixed lineage kinase domain-like protein

 https://www.genecards.org/cgi-bin/carddisp.pl?gene=MLKL&keywords=MLKL

PGAM5 S/T-protein phosphatase mitochondrial

https://www.genecards.org/cgi-bin/carddisp.pl?gene=PGAM5&keywords=PGAM5

Huom uusi tieto: PGAM5 on myös KEAP1 (Kelch proteiini) substraatti. Aiemmin on puhuttu vain NRF2 proteiinista KEAP1 substraattina!  Tätä  systeemiä täytyy ajatella!

 https://www.sciencedirect.com/science/article/pii/S2213231721003463

 DNM1L  Dynamin1like  (GTPase)

https://www.genecards.org/cgi-bin/carddisp.pl?gene=DNM1L&keywords=DNM1L

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