tetano
Editor, Senior Moderator
PNAS Nexus
. 2023 Sep 19;2(9)
gad282.
doi: 10.1093/pnasnexus/pgad282. eCollection 2023 Sep. Severe acute respiratory syndrome coronavirus 2 infection leads to Tau pathological signature in neurons
Cristina Di Primio[SUP] 1 [/SUP], Paola Quaranta[SUP] 1 2 [/SUP], Marianna Mignanelli[SUP] 3 [/SUP], Giacomo Siano[SUP] 3 [/SUP], Matteo Bimbati[SUP] 3 4 [/SUP], Arianna Scarlatti[SUP] 3 [/SUP], Carmen Rita Piazza[SUP] 2 5 [/SUP], Piero Giorgio Spezia[SUP] 2 [/SUP], Paola Perrera[SUP] 2 [/SUP], Fulvio Basolo[SUP] 6 [/SUP], Anello Marcello Poma[SUP] 6 [/SUP], Mario Costa[SUP] 1 [/SUP], Mauro Pistello[SUP] 2 7 [/SUP], Antonino Cattaneo[SUP] 3 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; Tau; neuro-COVID; phospho-Tau.
. 2023 Sep 19;2(9)
gad282.doi: 10.1093/pnasnexus/pgad282. eCollection 2023 Sep. Severe acute respiratory syndrome coronavirus 2 infection leads to Tau pathological signature in neurons
Cristina Di Primio[SUP] 1 [/SUP], Paola Quaranta[SUP] 1 2 [/SUP], Marianna Mignanelli[SUP] 3 [/SUP], Giacomo Siano[SUP] 3 [/SUP], Matteo Bimbati[SUP] 3 4 [/SUP], Arianna Scarlatti[SUP] 3 [/SUP], Carmen Rita Piazza[SUP] 2 5 [/SUP], Piero Giorgio Spezia[SUP] 2 [/SUP], Paola Perrera[SUP] 2 [/SUP], Fulvio Basolo[SUP] 6 [/SUP], Anello Marcello Poma[SUP] 6 [/SUP], Mario Costa[SUP] 1 [/SUP], Mauro Pistello[SUP] 2 7 [/SUP], Antonino Cattaneo[SUP] 3 [/SUP]
Affiliations
- PMID: 37731949
- PMCID: PMC10508204
- DOI: 10.1093/pnasnexus/pgad282
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.
Keywords: COVID-19; SARS-CoV-2; Tau; neuro-COVID; phospho-Tau.