1. Alzheimer's-like signaling in brains of COVID-19 patients
- Author
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Steve Reiken, Leah Sittenfeld, Haikel Dridi, Yang Liu, Xiaoping Liu, and Andrew R. Marks
- Subjects
Epidemiology ,SARS-CoV-2 ,Health Policy ,Brain ,COVID-19 ,Ryanodine Receptor Calcium Release Channel ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Post-Acute COVID-19 Syndrome ,Developmental Neuroscience ,Alzheimer Disease ,Humans ,Neurology (clinical) ,Calcium Signaling ,Geriatrics and Gerontology - Abstract
The mechanisms that lead to cognitive impairment associated with COVID-19 are not well understood.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 (Ca2We 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.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.
- Published
- 2021