# NF-κB as a driver of neurotoxic astrocytes in Alzheimers disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $431,750

## Abstract

PROJECT SUMMARY
Astrocytes participate in several intrinsic functions in brain areas deeply affected by Alzheimer's disease (AD).
Under physiological conditions, astrocytes modulate synaptic plasticity, provide nutrients and support for
neuronal survival, and contribute to higher cognitive functions and immune responses. However, astrocytes
lose their protective phenotype and become increasingly detrimental during neurodegenerative disorders.
Given the close association of astrocytes to brain disorders, it is surprising how little is known about the
pathological function of these cells in disease processes. In AD, astrocytes become increasingly prominent as
the disease progresses. We previously showed that these cells are highly plastic and can produce signals that
either exacerbate or mitigate AD pathogenesis, indicating that modulating astrocytic function could have
therapeutic value. Although mechanistic studies are yet to be developed, transcriptomic and proteomic
approaches have provided clues to the molecular processes that potentially drive the pathogenic properties of
astrocytes, with the nuclear factor-κB (NF-κB) being a promising candidate. NF-κB is a key transcriptional
regulator of inflammation that has been linked to many chronic immune-related diseases. Our proposal seeks
to use newly engineered genetic tools to investigate the hypothesis that chronic activation of astrocytic NF-κB
impairs brain function and drives AD pathogenesis. These studies will provide definitive evidence of the pivotal
role played by NF-κB in astrocytic function and its potential as a target to treat AD.
!

## Key facts

- **NIH application ID:** 10055202
- **Project number:** 1R21AG069081-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** FRANK M LAFERLA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $431,750
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055202

## Citation

> US National Institutes of Health, RePORTER application 10055202, NF-κB as a driver of neurotoxic astrocytes in Alzheimers disease (1R21AG069081-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10055202. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*