# BLR&D Research Career Scientist Award

> **NIH VA IK6** · CENTRAL ARKANSAS VETERANS HLTHCARE SYS · 2024 · —

## Abstract

Protein aggregation underlies most or all types of neurodegeneration and many
other age-progressive diseases. We have isolated and analyzed very pure aggregates
from Alzheimer’s Disease (AD), Parkinson’s Disease (PD); nematode models of
Huntington’s Disease (HD), AD, and PD; and human cell-culture models of AD. The
proteins that contribute to these aggregates show considerable overlap; for example,
>80% of proteins that are significantly more abundant in aggregates from AD than from
age-matched controls, are shared and concordant in amyloid plaque (containing Aβ1-42)
and in neurofibrillary tangles containing hyperphosphorylated tau), although these
aggregates have long been thought to be exclusively extracellular and intra-neuronal,
respectively. We recently performed novel cross-linking studies that defined the protein
interfaces that mediate adhesion within aggregates, and have screened drugs for their
ability to disrupt protein coalescence in vivo. Several drugs have the ability to reduce or
slow aggregate accrual, and one (PNR502) has been shown to reverse aggregation in
both mouse and nematode models of AD-like amyloidosis. We are currently in the
process of performing quantitative structure-activity studies to enable the generation of
2nd-generation drugs, further optimized for desirable drug properties. Two patents have
been filed (with both VA and affiliated-university participation) for subsets of active drugs;
the first of these addresses PNR502 and several of its structural analogs.

## Key facts

- **NIH application ID:** 10724243
- **Project number:** 5IK6BX004851-05
- **Recipient organization:** CENTRAL ARKANSAS VETERANS HLTHCARE SYS
- **Principal Investigator:** Robert Joseph Shmookler Reis
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10724243

## Citation

> US National Institutes of Health, RePORTER application 10724243, BLR&D Research Career Scientist Award (5IK6BX004851-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10724243. Licensed CC0.

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