# Developing a Drosophila Model of Parkinson’s Disease

> **NIH NIH R03** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $154,292

## Abstract

Parkinson’s disease (PD), known for over 2 centuries now, is the most common neurodegenerative movement
disorder with no known cure as yet. PD is also the fastest growing neurological disorder globally in prevalence,
disability and death and has devastating consequences to patients and families, in addition to the enormous
economic burden. The well-described neuropathological hallmarks of PD are locomotion deficits, loss of
dopaminergic neurons from substantia nigra and the formation of a-Synuclein (a-Syn) rich inclusions known as
Lewy bodies. Interestingly apart from a-Syn, another highly conserved and very poorly understood family of
human Tubulin-binding proteins, called the Tubulin Polymerization Promoting Proteins (TPPP) is implicated in
PD and other synucleinopathies. Human TPPP is reported to have aggregation promoting properties and is a
constituent in pathological protein deposits together with a-Syn in PD and related disorders such as Lewy body
dementia and multiple systems atrophy. Importantly, there are no published knockout studies of any
mammalian TPPP yet to better understand the genetics and neuropathology that might link TPPP aggregation
and neurotoxicity to the pathogenesis of PD. Recently, we discovered the only Drosophila homolog of human
TPPP named Ringmaker (Ringer) from a large-scale forward genetic screen. Our preliminary studies revealed
that the adult TPPP/ringer mutants display reduced lifespan, severe locomotor disabilities, loss of
dopaminergic neurons and deficits in mitochondrial structure and function. All of these phenotypes of ringer
mutants resemble some of the salient features of human PD patients. The overall objective of this proposal is
to develop a new model of PD utilizing Drosophila ringer mutants. Our central hypothesis is that Drosophila
Ringer plays a key role in mitochondrial function and neurodegeneration. The hypothesis will be tested in two
independent Specific Aims using genetic, cell biological, biochemical and behavioral experiments. In Aim 1, we
will examine the progressive nature of the loss of DA neurons as well as other neuronal subtypes impacted in
ringer mutant brain in addition to presence of any neuronal inclusions or aggregates. In Aim 2, we will explore
the role of Ringer in mitochondrial structure and function and establish what role ringer might play with known
PD-related a-Syn, pink1 and parkin genes. The proposal is highly innovative, feasible and timely, as it will
utilize the only available in vivo Drosophila ringer mutant model to investigate its role in neurodegeneration and
characterize the neuropathological phenotypes as well as explore its genetic and molecular underpinnings to
provide insights into the role of human TPPP in PD and related neurodegenerative disorders. Importantly, this
research will address a critical gap in our understanding of how this risk gene might contribute to exert toxicity
in the brains of PD patients. Mechanistic insights gained from these studies,...

## Key facts

- **NIH application ID:** 9957906
- **Project number:** 1R03NS116308-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Swati Banerjee
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $154,292
- **Award type:** 1
- **Project period:** 2020-04-15 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957906

## Citation

> US National Institutes of Health, RePORTER application 9957906, Developing a Drosophila Model of Parkinson’s Disease (1R03NS116308-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9957906. Licensed CC0.

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