# Defining the Role of Poly ADP-ribose in Biomolecular Condensation in ALS and FTLD

> **NIH NIH RF1** · JOHNS HOPKINS UNIVERSITY · 2020 · $2,593,144

## Abstract

PROJECT SUMMARY
Poly ADP-ribose (PAR) is an RNA-like protein modification whose dysregulation is linked to age-
dependent neurodegenerative diseases including ALS, Parkinson’s and Alzheimer’s disease.
PAR is a core component of stress granules, a type of membraneless ribonucleoprotein (RNP)
granules that can seed aberrant protein aggregation leading to neuropathology. Unlike RNA, PAR
can form into both linear and branched structures. Strikingly, inhibitors of PAR polymerase, which
is a class of FDA-approved anticancer drugs, were shown to mitigate neurotoxicity in cell models
of neurodegeneration, reflecting a potential role of PAR in neurotoxicity. Two laboratories at Johns
Hopkins University led by Sua Myong (Biophysics department) and Anthony K. L. Leung
(Department of Biochemistry and Molecular Biology ) bring together orthogonal expertise in
molecular imaging, chemical and proteomic methods to investigate the molecular basis of PAR-
driven protein condensation and aggregation mechanism responsible for neurodegenerative
diseases, which may pave new ways of developing therapy. Our recent discovery of a PAR
modifying method (Leung et al, Mol Cell, 2019) and mechanism of FUS liquid-liquid phase
separation in ALS/FTLD-linked cases (Myong et al, Mol Cell, 2019) places us in an ideal position
for tackling the poorly understood role of PAR in biomolecular condensation implicated in
neurodegenerative diseases. In Preliminary Studies, we discovered that (i) PAR is extremely
potent in condensing FUS (fused in sarcoma), an RNA binding protein localized in stress granules
and implicated in ALS/FTLD and (ii) PAR targeted proteome is enriched in stress granule
components. Building on these exciting results, we propose to uncover the role of PAR in driving
biomolecular condensation by employing single molecule, biochemical, meso-scale, biophysical
and cellular platforms.

## Key facts

- **NIH application ID:** 10157522
- **Project number:** 1RF1AG071326-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Anthony K L Leung
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,593,144
- **Award type:** 1
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157522

## Citation

> US National Institutes of Health, RePORTER application 10157522, Defining the Role of Poly ADP-ribose in Biomolecular Condensation in ALS and FTLD (1RF1AG071326-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10157522. Licensed CC0.

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