# Role and targeting of PRMT5 in prostate cancer

> **NIH NIH R01** · PURDUE UNIVERSITY · 2021 · $375,488

## Abstract

Project Summary/Abstract
Alzheimer’s disease (AD) is a major neurodegenerative disease affecting millions of people with no cure. There
is an urgent need to identify potential causes and mediators that may contribute to AD onset to advance
preventive strategy. Emerging evidence suggested that epigenetic regulation of gene expression in human
neurons is a major mechanism in AD pathogenesis. Protein Arginine Methyltransferase 5 (PRMT5) has been
recognized as a critical epigenetic regulator that transmits extracellular signaling (e.g., stress) into gene
expression. High PRMT5 expression is found in human neurons, whereas PRMT5 expression is decreased in
AD patients. Knockdown of PRMT5 significantly increases apoptosis of neuronal cell lines over-expressing the
AD-related Swedish mutation of the human amyloid-β precursor protein. We have observed, under the current
R01 support, that PRMT5 is required for the survival of NE-like cells, a neuron-like cancer cells in prostate cancer.
Given that PRMT5 has emerged as an oncogene and that targeting PRMT5 with small molecule inhibitors for
the treatment of several human cancers is in clinical trials, it is critically important to define the role of PRMT5 in
human neurons to prevent treatment-induced damages to neurons and the development of AD-like dementia. In
this proposed study, Hu and Yang lab take advantage of neurons derived from healthy and AD human induced
pluripotent stem cells (hiPSCs) carrying AD susceptible genetic risk factors to tackle this problem. We
hypothesize that PRMT5 provides a survival signal in NE-like cells and human neurons via epigenetic regulation
of its target gene expression and that reduced expression/activity of PRMT5 in neurons leads to neuronal death
and development of AD phenotypes. We will test this hypothesis with the following aims. Aim 1. To elucidate
the protective role of PRMT5 in NE-like cells and human AD neurons via epigenetic regulation of gene
expression. By completion of this aim, we will gain a deep understanding of the shared and distinct protective
roles of PRMT5 in NE-like cells vs in neurons carrying AD susceptible genetic risk factors. Aim 2. To determine
the tolerability of human healthy and AD neurons in responses to PRMT5 inhibition. Findings from this
aim may provide evidence that targeting PRMT5 for cancer treatment would cause potential toxicities to human
neurons and the development of AD-related neuropathology. The results obtained from this Administrative
Supplement will provide knowledge regarding how PRMT5 serves a shared or distinct protective role in NE-like
cells and neurons carrying AD genetic risk factors to halt the neurotoxicity of AD. Our study evaluates the
consequences of PRMT5 inhibition/knockdown on healthy and AD neurons carrying AD genetic risk factors,
shedding light on strategies to prevent PRMT5-based cancer therapeutics-related impairment of neurocognitive
functions including AD-like dementia.

## Key facts

- **NIH application ID:** 10288726
- **Project number:** 3R01CA212403-05S1
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** CHANG-DENG HU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $375,488
- **Award type:** 3
- **Project period:** 2017-06-09 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288726

## Citation

> US National Institutes of Health, RePORTER application 10288726, Role and targeting of PRMT5 in prostate cancer (3R01CA212403-05S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10288726. Licensed CC0.

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