# The Norepinephrine transporter as a therapeutic target for treatment of alpha-synuclein pathology in PD

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2021 · $419,375

## Abstract

The Norepinephrine transporter as a therapeutic target for treatment of alpha-synuclein
 pathology in PD
Parkinson’s disease (PD) is a neurodegenerative disorder prevalent in ~1% of the population,
making it a medically important problem, especially in the aging population. The economic burden
for PD exceeds $10 Billion annually in the US and the prevalence of PD is projected to significantly
increase in the coming decades. PD is characterized by severe motor deficits as well as non-
motor symptoms such as loss of smell, constipation and cognitive disability. Sporadic PD is
characterized by widespread alpha-synuclein (α-syn) positive inclusions called Lewy bodies and
neurites in the brain, along with loss of dopamine neurons of the substantia nigra pars compacta
(SNpc). However, the underlying mechanisms of α-syn mediated pathogenesis, progression, and
neurodegeneration are still not clear. Consequentially, strategies for treating pathogenesis and
progression of sporadic PD have not been well developed. Previous studies and our preliminary
data suggest that the norepinephrine transporter (NET) is a potential therapeutic target for α-syn
pathology in PD. Our overall hypothesis is that genetic deletion or pharmacological inhibition of
NET will reduce α-Syn propagation, neurodegeneration, neuroinflammation and behavioral
deficits. We will test our hypothesis through two aims. In aim1, we will test the effect of NET
deletion or inhibition on histological markers of α-syn aggregation and propagation, dopamine
neurodegeneration and neuroinflammation. In aim2, we will test the effect of NET deletion or
inhibition on motor deficits.
The proposed experiments will not only provide an insight into the underlying mechanism of α-
syn propagation and vulnerability, but more importantly reveal a potential therapeutic strategy for
ameliorating functional impairments and slow progression of PD pathology.

## Key facts

- **NIH application ID:** 10195789
- **Project number:** 1R21NS121976-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Nikhil Urs
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $419,375
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195789

## Citation

> US National Institutes of Health, RePORTER application 10195789, The Norepinephrine transporter as a therapeutic target for treatment of alpha-synuclein pathology in PD (1R21NS121976-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10195789. Licensed CC0.

---

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