Abstract
Introduction: The mechanisms that lead to cognitive impairment associated with COVID-19 are not well understood.
Methods: Brain lysates from control and COVID-19 patients were analyzed for oxidative stress and inflammatory signaling pathway markers, and measurements of Alzheimer’s disease (AD)-linked signaling biochemistry. Post-translational modifications of the ryanodine receptor/calcium (Ca2 + ) release channels (RyR) on the endoplasmic reticuli (ER), known to be linked to AD, were also measured by co-immunoprecipitation/immunoblotting of the brain lysates.
Results: We provide evidence linking SARS-CoV-2 infection to activation of TGF-β signaling and oxidative overload. The neuropathological pathways causing tau hyperphosphorylation typically associated with AD were also shown to be activated in COVID-19 patients. RyR2 in COVID-19 brains demonstrated a “leaky” phenotype, which can promote cognitive and behavioral defects.
Discussion: COVID-19 neuropathology includes AD-like features and leaky RyR2 channels could be a therapeutic target for amelioration of some cognitive defects associated with SARS-CoV-2 infection and long COVID.
Keywords: Alzheimer’s disease; COVID-19; calcium; ryanodine receptor; tau pathology.
【저자키워드】 COVID-19, Alzheimer's disease, calcium, ryanodine receptor, tau pathology., 【초록키워드】 pathology, Biochemistry, SARS-COV-2 infection, oxidative stress, Brain, COVID, Neuropathology, pathway, Alzheimer's disease, Cognitive impairment, phenotype, disease, calcium, mechanism, COVID-19 patients, post-translational modifications, TGF-β, Signaling, Evidence, COVID-19 patient, therapeutic target, lead, cognitive, Activation, lysates, Modification, lysate, feature, Ryanodine, hyperphosphorylation, RyR2, inflammatory signaling, oxidative, shown, analyzed, include, activated, demonstrated, promote, with COVID-19, 【제목키워드】 Brain, Signaling, COVID-19 patient,