# PHF15, a potential repressor of inflammation in the brain and its relevance to Alzheimer's disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $194,295

## Abstract

Abstract
 While genetic risk factors for Alzheimer’s disease (AD) have been identified, around ninety percent of
patients are sporadic cases. Therefore, in this proposal, we seek to understand the molecular mechanisms
behind the establishment of sporadic cases of AD. Recently, we have found that a putative epigenetic
regulator, PHD finger 15 (PHD15), is a transcriptional repressor of genes regulating inflammation in microglia.
Indeed, knockout of Phf15 in mouse microglial cells was sufficient to increase pro-inflammatory mediators and
anti-viral genes, of note, including amyloid precursor protein (APP) and complement factors, in the absence of
any stimuli. Because the mRNA expression of PHF15 in human and mouse microglia is increased upon
healthy aging, we hypothesize that PHF15 epigenetically represses age-induced inflammation in microglia and
that failure to up-regulate PHF15 results in neuroinflammation and cognitive decline. To test our hypothesis,
we will identify members of the protein complex containing PHF15 by mass-spectrometry using a human
microglial cell line that we have established. After confirming protein binding using biochemical assays, we will
perform functional assays by establishing gain- and loss-of-function cell lines to validate whether the identified
complex proteins cooperate with PHF15 to repress inflammation. In addition to isolating the PHF15 protein
complex, we will also try to identify non-genetic factors that prevent PHF15 mRNA up-regulation using both in
vivo and in vitro models. Based on our preliminary data, we will focus on virus infection and high-fat diet for the
in vivo experiments, as well as oxidative stress and infection mimics (ligands for toll-like receptors and
inflammasomes) for the in vitro experiments. Overall, the goals of this proposal are to determine the molecular
mechanism behind how PHF15 represses inflammation in microglia and to identify non-genetic factors that
prevent up-regulation of PHF15 expression. These results may help us to better understand the causes of
sporadic cases of AD and, thus, direct the development of treatment strategies to treat and/or prevent this
disease.

## Key facts

- **NIH application ID:** 10477295
- **Project number:** 5R21AG073735-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Kaoru Saijo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,295
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477295

## Citation

> US National Institutes of Health, RePORTER application 10477295, PHF15, a potential repressor of inflammation in the brain and its relevance to Alzheimer's disease (5R21AG073735-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10477295. Licensed CC0.

---

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