# PROTEOMIC MAPPING OF PATHOLOGICAL INTERACTIONS ACROSS THE SYNUCLEINOPATHY BRAIN

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2022 · $276,500

## Abstract

Summary Statement
The cellular processes responsible for Lewy pathology (LP) formation, maturation, and clearance in
human disease tissues remain unknown in part because a lack of techniques available to capture LP
interactions in the intact cellular environment. The long-term goal is to determine the core-cellular
processes responsible for LP in the human brain and find therapeutic targets to develop disease
modifying treatments for synucleinopathy. The objective of this proposal is to determine the role of LP
interactions in the initiation and progression of synucleinopathies. The central hypothesis is that core
molecular LP interactions are the major determinants of clinical synucleinopathies phenotypes and
disease progression. Our rationale for the proposed studies is that determining LP interactions across
the neuroaxis of the diseased brain will reveal those core pathological processes responsible for human
synucleinopathies and offer a concrete molecular description concerning how those processes define,
distinguish, and treat clinical synucleinopathies. The central hypothesis will be tested in two specific
aims: 1) Determine LP interactions in the human synucleinopathy brain; 2) Investigate LP interactions
across the neuroaxis of a rodent brain as synucleinopathy develops. We will test these aims by using our
innovative in situ proximity labeling technique that overcomes previous technical limitations, to provide
a clear molecular understanding of LP. The proposed research is significant because it will provide a
detailed understanding of LP interactions that should be targets for future disease modifying
therapeutics. The expected outcome of the proposed research is to provide the field with an unbiased
account of LP interactions in the human diseased brain and in models of synucleinopathy. These results
will have an immediate positive impact because they will provide a “big picture” cellular/molecular
understanding of human synucleinopathies that is currently unavailable but crucial for progress in the
field

## Key facts

- **NIH application ID:** 10504875
- **Project number:** 1R01NS128467-01
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Bryan Killinger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $276,500
- **Award type:** 1
- **Project period:** 2022-08-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10504875

## Citation

> US National Institutes of Health, RePORTER application 10504875, PROTEOMIC MAPPING OF PATHOLOGICAL INTERACTIONS ACROSS THE SYNUCLEINOPATHY BRAIN (1R01NS128467-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10504875. Licensed CC0.

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