A Precision high content screening assay for AB-mediated neuronal cell cycle reentry

NIH Pandemic-Era Grants

Pandemic Era Grants

2020

Document text

Principal Investigator: ELIZABETH  SHARLOW
Organization: UNIVERSITY OF VIRGINIA
Fiscal Year: 2020
Award: $161,500
Funding agency: National Institute on Aging

Project Summary
We have established a human iPS-derived neuronal-glial cell model system that we are
using to (1) study AβO-induced neuronal cell cycle reentry (CCR) as well as (2) screen
for compounds that inhibit AβO-induced neuronal CCR. We now propose to adapt this
cell-based model system to evaluate the effects on SARS-CoV-2 spike protein-ACE2
binding on neuronal “fitness”, responsiveness and intracellular signaling as well as use to
screen for small molecule inhibitors that may used for the next generation SARS-CoV-2
therapeutics.

Terms: <2019 novel coronavirus><2019-nCoV><A β-42><A β42><A-beta 42><A-beta42><AD dementia><Abeta-42><Abeta42><Administrative Supplement><Alzheimer><Alzheimer Type Dementia><Alzheimer beta-Protein><Alzheimer disease><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Amyloid beta-Protein><Alzheimer's Disease><Alzheimer's amyloid><Alzheimer's disease dementia><Alzheimers Dementia><Alzheimers disease><Amyloid><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Protein A4><Amyloid Substance><Amyloid beta-42><Amyloid beta-Protein><Amyloid beta42><Amyloid β><Amyloid β-42><Amyloid β-Peptide><Amyloid β-Protein><Amyloid β42><Amyloidβ-42><Amyloidβ42><Angiotensin Converting Enzyme><Angiotensin I-Converting Enzyme><Assay><Aβ><Aβ-42><Aβ42><Binding><Binding Proteins><Bioassay><Biologic Assays><Biologic Models><Biological><Biological Assay><Biological Models><Brain><Brain Nervous System><CD143 Antigens><CNS Nervous System><COVID-19><COVID19><Carboxycathepsin><Cell Body><Cell Communication and Signaling><Cell Cycle><Cell Division Cycle><Cell Signaling><Cells><Central Nervous System><Cessation of life><Cleaved cell><Data><Death><Development><Dipeptidyl Peptidase A><Distress><Drugs><Dysfunction><Encephalon><End Point Assay><Endpoint Assays><Event><FDA approved><Failure><Functional disorder><Future><Glia><Glial Cells><Human><Intracellular Communication and Signaling><Isoforms><Kininase A><Kininase II><Kolliker's reticulum><Ligand Binding Protein><Ligand Binding Protein Gene><Mediating><Medication><Model System><Modern Man><Molecular Interaction><Nerve Cells><Nerve Unit><Neural Cell><Neuraxis><Neurocyte><Neuroglia><Neuroglial Cells><Neuronal Dysfunction><Neurons><Non-neuronal cell><Nonneuronal cell><Patients><Peptides><Peptidyl-Dipeptidase A><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacodynamics><Physiopathology><Primary Senile Degenerative Dementia><Protein Binding><Protein Isoforms><Protein Subunits><Proteins><Reporting><SARS Virus><SARS corona virus><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe acute respiratory syndrome coronavirus 2><Signal Transduction><Signal Transduction Systems><Signaling><Symptoms><System><Therapeutic><Viral><Viral Antigens><Virus><Wuhan coronavirus><a beta peptide><abeta><amyloid beta><amyloid-b protein><associated symptom><base><beta amyloid fibril><biological signal transduction><bound protein><cleaved><co-morbid symptom><co-occuring symptom><comorbid symptom><concurrent symptom><cooccuring symptom><corona virus disease 2019><coronavirus disease 2019><dementia of the Alzheimer type><developmental><drug/agent><fitness><iPS><iPSC><iPSCs><induced pluripotent stem cell><inhibitor><inhibitor/antagonist><nerve cell death><nerve cell loss><nerve cement><neural dysfunction><neuron cell death><neuron cell loss><neuron death><neuron loss><neuron toxicity><neuronal><neuronal cell death><neuronal cell loss><neuronal death><neuronal loss><neuronal toxicity><neurotoxic><neurotoxicity><next generation><pathophysiology><prevent><preventing><primary degenerative dementia><response><screening><senile dementia of the Alzheimer type><severe acute respiratory syndrome-CoV><small molecule inhibitor><soluble amyloid precursor protein><symptom association><symptom comorbidity><virus antigen>