# PERK Dependent Mechanisms of Neuroinflammation

> **NIH NIH R01** · WEST VIRGINIA UNIVERSITY · 2021 · $328,125

## Abstract

Neurological diseases are a growing public health concern with no cures and few treatments.
Inflammation in the central nervous system (neuroinflammation) is observed in most neurological diseases and
is thought to contribute to neuropathology. Our long-term goal is to identify targets for selective regulation of
pathological inflammation in the CNS. Endoplasmic reticulum (ER) stress in neuronal and glial cells is
associated with most neurodegenerative diseases. ER stress also drives inflammation, however the underlying
mechanisms and impact on disease are unknown. Our central hypothesis is that PERK signaling in astrocytes
contributes to neuroinflammation. This will be tested in three specific aims. 1) Determine the molecular
mechanisms of PERK-dependent signaling leading to neuroinflammatory gene expression. Using traditional
cellular and molecular biology and hypothesis-driven transcriptomics, the mechanisms of PERK-dependent
neuroinflammation will be elucidated. 2) Determine the mechanisms by which PERK deletion affects
neuroinflammation in vivo. Using in vivo cell-specific RNA labeling and conditional knockout mice we will define
the spatial and temporal occurrence of ER stress and inflammatory gene expression in astrocytes, and how
astrocyte-specific knockout of PERK affects the neuroinflammatory disease of experimental autoimmune
encephalomyelitis. 3) Determine the non-cell autonomous mechanisms of ER stress signaling in astrocytes.
Using in vitro primary cell co-cultures and in vivo conditional knockout mice, the PERK-dependent effects of
astrocytes on the function and viability of resident and infiltrating cells of the CNS will be established. This
project is significant because it will define basic mechanisms driving neuroinflammation and establish a
potential therapeutic target for immune modulation in the CNS.

## Key facts

- **NIH application ID:** 10146490
- **Project number:** 5R01NS099304-05
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Gordon P. Meares
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,125
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146490

## Citation

> US National Institutes of Health, RePORTER application 10146490, PERK Dependent Mechanisms of Neuroinflammation (5R01NS099304-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10146490. Licensed CC0.

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