# The integrated stress response in cognitive disorders

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $911,165

## Abstract

ABSTRACT
Cognitive disorders pose a major threat to public health, and represent an enormous economic and social
burden. Despite the high incidence of these disorders, effective treatments remain severely limited. Thus, the
development of novel therapeutic to treat cognitive disorders is an important goal. Here we focus on the
integrated stress response (ISR), a conserved signaling network that restores protein homeostasis by
regulating protein synthesis, and a main causative pathway underlying the memory deficits associated with a
wide range of cognitive disorders. The goal of this competing renewal is to define the precise molecular,
cellular, and circuit mechanisms by which activation of the ISR leads to cognitive dysfunction. In Aim 1, we will
generate and characterize mice carrying a human mutation in a key component of the ISR, which activates the
ISR, and is associated with intellectual disability. In Aim 2, we will generate and use state-of-the-art, novel molecular-
genetic approaches to identify the specific cell types in the brain driving the long-term memory deficits upon
activation of the ISR. Finally, in Aim 3, we will develop a novel high-throughput screening platform to identify new
inhibitors of the ISR. The results of these Aims will provide new fundamental insights into the biological basis
of cognitive dysfunction and hold the hope of opening new therapeutic avenues for cognitive disorders resulting
from perturbation of protein homeostasis.

## Key facts

- **NIH application ID:** 10156715
- **Project number:** 2R01NS076708-10
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Mauro Costa-Mattioli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $911,165
- **Award type:** 2
- **Project period:** 2012-03-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156715

## Citation

> US National Institutes of Health, RePORTER application 10156715, The integrated stress response in cognitive disorders (2R01NS076708-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10156715. Licensed CC0.

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