# Role of PLD3 in nucleic acid recognition and brain function

> **NIH NIH R56** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $443,750

## Abstract

This is a R01 proposal to study the function of Phospholipase D3 (PLD3) and its contribution to
neurodegeneration in mouse models. PLD3 missense mutations and under expression have been
implicated in Alzheimer's disease (AD) and in Spinocerebellar Ataxia, but the mechanisms by
which these mutations alter function are unclear. PLD3 protein is associated with neuritic AD
plaques and has been implicated in Ab and Tau processing. We have recently discovered that
PLD3 and a related protein PLD4 are not phospholipases, as was thought, but are in fact single-
stranded DNA and RNA exonucleases localized in endolysosomes. PLD3 and PLD4 can strongly
influence nucleic acid recognition by toll-like receptors (TLR) 7,8 and 9. Mice lacking both PLD3
and PLD4 enzymes die of massive autoinflammation, whereas the phenotype of Pld3–/– mice is
relatively subtle and has not been investigated in older mice. Here we propose to study the roles
of PLD3 in more detail by evaluating functional alterations of disease associated PLD3 alleles
and by generating tools to assess the effects of deficiency of PLD3 and PLD4 in microglia and
other tissues of the brain.

## Key facts

- **NIH application ID:** 10388543
- **Project number:** 1R56AG070775-01
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** DAVID NEMAZEE
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $443,750
- **Award type:** 1
- **Project period:** 2021-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388543

## Citation

> US National Institutes of Health, RePORTER application 10388543, Role of PLD3 in nucleic acid recognition and brain function (1R56AG070775-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10388543. Licensed CC0.

---

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