COVID-19 has represented an issue for global health since its outbreak in March 2020. It is now evident that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer’s disease. Little is known about the molecular basis of these manifestations. Here, several strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated on cellular extracts, subcellular fractions, and brain tissue. The viral proteins spike, nucleocapsid, and membrane were overexpressed in SH-SY5Y cells, and the direct interaction and effect on Tau phosphorylation were checked using immunoblot experiments. Upon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer’s disease and other tauopathies. Moreover, this event increases Tau’s propensity to form insoluble aggregates and alters its subcellular localization. Our data support the hypothesis that SARS-CoV-2 infection in the central nervous system triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.

Severe acute respiratory syndrome coronavirus 2 infection leads to Tau pathological signature in neurons

Cristina Di Primio
;
Marianna Mignanelli;Giacomo Siano;Arianna Scarlatti;Mario Costa
;
Mauro Pistello;Antonino Cattaneo
2023

Abstract

COVID-19 has represented an issue for global health since its outbreak in March 2020. It is now evident that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer’s disease. Little is known about the molecular basis of these manifestations. Here, several strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated on cellular extracts, subcellular fractions, and brain tissue. The viral proteins spike, nucleocapsid, and membrane were overexpressed in SH-SY5Y cells, and the direct interaction and effect on Tau phosphorylation were checked using immunoblot experiments. Upon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer’s disease and other tauopathies. Moreover, this event increases Tau’s propensity to form insoluble aggregates and alters its subcellular localization. Our data support the hypothesis that SARS-CoV-2 infection in the central nervous system triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.
2023
Settore BIO/09 - Fisiologia
SARS-CoV-2; COVID-19; neuro-COVID; Tau; phospho-Tau
   Centro Nazionale per lo sviluppo di terapia genica e farmaci con tecnologia a RNA
   MUR
   PNRR

   Neurodegeneration
   MUR
   PNRR

   TUSCANY HEALTH Ecosystem
   THE
   MUR
   PNRR
   ECS_00000017

   Extended Partnership initiative on Emerging Infectious Diseases
   MUR
   PNRR
   PE00000007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11384/133502
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