# Bladder Dysfunction and Dysregulation of Neurotransmission

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2024 · —

## Abstract

Bladder dysfunction is a common, distressing finding in patients afflicted with two
disorders that are increasingly prevalent in the general population but significantly over-
represented in the veteran population—type 2 diabetes (T2DM) and Parkinson’s disease (PD).
Currently, treatments for bladder dysfunction address the symptoms, not the cause, which
remains largely unknown. Though bladder dysfunction manifests early in the course of each
disease, it frequently remains unrecognized and worsens with disease progression. T2DM and
PD can occur independently, however these disorders are related and sometimes coincident. It
has been shown that T2DM increases the risk of PD, and PD patients with T2DM develop more
aggressive motor and cognitive impairment. Such reciprocity is likely to spring from a common
biochemical mechanism underlying the pathogenesis of both chronic diseases, with adverse
consequences for bladder function. The pathology of PD is associated with aggregation of alpha
synuclein (αSyn), a protein abundant in presynaptic nerve varicosities whose biological function,
though incompletely understood, encompasses a role in facilitation of neurotransmission. In this
proposal, we present and rigorously test our proposed mechanism of αSyn interaction with the
unconventional motor protein, myosin 5a (Myo5a), as well as with cytoskeletal actin, in functional
processes involving neurotransmission and glucose regulation in the bladder. We will examine
perturbation of this mechanism in both T2DM and PD animal models and under in vitro
hyperglycemic conditions. We also propose to investigate the influence of glucagon-like peptide
agonists, agents used in T2DM treatment, on restoring the αSyn-Myo5a-actin axis. The
multidisciplinary studies proposed herein will integrate biochemical, molecular, cellular and
physiological approaches that exploit state of the art methods combined with proven conventional
techniques. The information gained will provide a foundation for more effective interventions
addressing the foundational causes of bladder dysfunction and deficits in bladder
neurotransmission in patients with T2DM and PD.

## Key facts

- **NIH application ID:** 10720894
- **Project number:** 5I01BX001790-10
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** MARYROSE P SULLIVAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-01-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10720894

## Citation

> US National Institutes of Health, RePORTER application 10720894, Bladder Dysfunction and Dysregulation of Neurotransmission (5I01BX001790-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10720894. Licensed CC0.

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