# PERK determines polarized targeting of growth factors in neurons

> **NIH NIH R21** · DREXEL UNIVERSITY · 2021 · $250,948

## Abstract

Abstract:
This competitive revision will extend the original grant “PERK determines polarized targeting of growth factors
in neurons” (1R21AG063029), to explore how human genetic variants in Alzheimer’s disease–linked genes,
including PERK, affect neuronal sensitivity to SARS-CoV-2 infection. A significant number of AD/tauopathy
genes either contribute to the secretory function of cells (when wild type), or disrupt it and cause ER stress and
translational silencing (when mutated or damaged). On the other hand, coronaviruses subvert the host cell ER
and translational machinery to produce their own proteins. Thus, AD alleles that impact these pathways are
hypothesized here to also impact replication of the novel SARS-CoV-2 and the progression of COVID-19.
Genetic variants that fit this hypothesis will be identified (Aim 1) by relating the exomes of COVID-19 patients
at Geisinger’s Health Center to their longitudinal neurological presentation. Because PERK represents one
such gene that is already known to both be required for SARS coronavirus infection and to harbor hypomorphic
alleles that are a validated risk factor for AD/tauopathy, we will measure (Aim 2) the dependence of SARS-
CoV-2 Spike and 3a proteins biosynthesis, and the survival of neurons expressing them, on AD/tauopathy
variants in the PERK kinase pathway. Variants such as hypomorphic PERK alleles will be one likely
mechanistic explanation for the wide variation in sensitivity to COVID-19. Future work will validate, by cellular
and molecular approaches, other AD genes identified in Aim 1 as affecting COVID-19. In addition to testing the
genetic connection of AD/tauopathy alleles to altered risk for COVID-19 and neurological complications, our
studies will test small molecule drugs that can affect virus production and are also candidates for treatment of
neurodegeneration.

## Key facts

- **NIH application ID:** 10230823
- **Project number:** 3R21AG063029-01A1S1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** TALI GIDALEVITZ
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $250,948
- **Award type:** 3
- **Project period:** 2020-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230823

## Citation

> US National Institutes of Health, RePORTER application 10230823, PERK determines polarized targeting of growth factors in neurons (3R21AG063029-01A1S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10230823. Licensed CC0.

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