# The IL-6 Induced Retinal Iron Sequestration Response

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $406,042

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of the proposed studies is to define an IL6 triggered cellular iron sequestration response (CISR)
in a mouse model of Alzheimer's Disease (AD). Iron is necessary for growth and survival for all life forms,
so cellular iron uptake and sequestration is a mechanism that limits the growth of extracellular bacteria.
However, when the CISR is maladaptively activated by chronic neuroinflammation, the resulting iron
accumulation can be toxic to the CNS. Toxic iron accumulation and dysregulation have been implicated
in AD pathogenesis, and an ongoing phase 2 clinical trial is evaluating an iron chelator in AD patients
(NCT03234686). However, understanding the mechanisms leading to iron dysregulation, and the brain
cell types affected is likely to lead to a more targeted therapy than iron chelation. Evidence implicating
an IL6 induced CISR in AD pathogenesis includes: 1)AD brains have iron dysregulation, with iron
accumulation in plaques 2) AD brains have elevated IL6 levels near plaques.
overexpressing
elevated
neurodegeneration
Brain
as
in
3)A transgenic mouse
IL6 i n astrocytes has brain iron accumulation. 4)The 5XFAD mouse model of AD has
brain iron levels and CISR activation. 5) The iron chelator deferoxamine can ameliorate the
phenotype of the AD 
 mode l App/Ps1, another model driven by Aβ deposition. 6)
iron dysregulation is also associated with Parkinson's Disease and t he hereditary diseases classified
Neurodegenerations with Brain Iron Overload (NBIA). 
 Understanding the role of the IL6 induced CISR
AD pathogenesis is thus likely to lead to novel therapeutics for patients suffering from this disease.

## Key facts

- **NIH application ID:** 10281696
- **Project number:** 3R01EY028916-02S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** JOSHUA L DUNAIEF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $406,042
- **Award type:** 3
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10281696

## Citation

> US National Institutes of Health, RePORTER application 10281696, The IL-6 Induced Retinal Iron Sequestration Response (3R01EY028916-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10281696. Licensed CC0.

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