# Role of the circadian protein Nocturnin in modulating oxidative stress in substantia nigra dopaminergic neurons

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $450,375

## Abstract

Abstract
 Parkinson’s disease (PD) is the second most common neurodegenerative disease and is
characterized by severe movement disorders that result from selective loss of dopamine
neurons from the substantia nigra in the midbrain. In addition to the movement disorders, the
most common non-motor manifestation of PD is a major disruption in sleep-wake cycles, with
~80% of patients exhibiting excessive daytime sleepiness or changes in sleep timing and
reduced circadian amplitudes. The cause of the selective dopaminergic cell death is not known
but appears to be through various cellular insults that result in toxic aggregation of the a-
synuclein protein and increased oxidative stress. Although the existing data make difficult to
determine whether oxidative stress or protein aggregation is the initiating event, these two
processes clearly impact each other, and a growing body of evidence implicates oxidative stress
as being involved in at least the propagation of cellular injury that leads to neuropathology in
PD. In this exploratory application, we will explore the role of the circadian protein Nocturnin in
the pathogenesis of PD. Our data suggest that Nocturnin is an important modulator of oxidative
stress, with higher levels exacerbating stress and lower levels providing protective effects.
Nocturnin has been reported to be upregulated in the substantia nigra in PD patients suggesting
that it may be playing a role in excessive oxidative stress responses that contribute to
pathogenesis and we will examine this link through mechanistic work in both cells and mice in
this proposal. There are currently no treatments that prevent neuronal cell loss in PD and we
hypothesize that reduction of oxidative stress through the inhibition of Nocturnin might break
the cycle of cell death.

## Key facts

- **NIH application ID:** 10066683
- **Project number:** 1R21NS115482-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Carla B. Green
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,375
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066683

## Citation

> US National Institutes of Health, RePORTER application 10066683, Role of the circadian protein Nocturnin in modulating oxidative stress in substantia nigra dopaminergic neurons (1R21NS115482-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10066683. Licensed CC0.

---

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