# TMEM230 and Neurodegeneration in Parkinson's Disease

> **NIH NIH R01** · FLORIDA INTERNATIONAL UNIVERSITY · 2020 · $346,625

## Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by progressive degeneration
of dopaminergic neurons in the midbrain. At present, PD is incurable. A roadblock halting development of
effective therapy for PD is the limited understanding of PD pathogenesis. While most PD cases are sporadic
without an ascertained cause, about 10% of PD cases are likely caused by mutation of a known or unknown
gene. Genetic clues not only help define the molecular pathways leading to neurodegeneration but also help
identify biomarkers for monitoring disease progression and therapeutic effectiveness. Compared to the other
neurodegenerative diseases, genetic discovery for PD is significantly deferred. One reason for deferred genetic
discovery in PD is the incomplete penetrance of disease phenotypes in PD and it is particularly true for late-onset PD. A compelling need for PD research is identifying and validating the genes segregating with late-onset
PD. Recently the new gene TMEM230 was reported to cosegregate with disease in a large family affected by
late-onset PD. Once after a novel disease gene is identified, enormous efforts are required to validate the
authenticity of the pathogenic role of the mutant gene in the disease. First, genetic variants cosegregating with
the disease must be verified in independent families afflicted with the disease. Second, disease phenotypes
observed in patients carrying the genetic variant must be reproduced in animal models expressing the disease-associated mutation. Third, mechanistic studies must be fulfilled to reveal how the disease-linked mutation
impairs cellular functions and thus to determine how these new mechanisms are integrated into existing
pathways leading to cell death in the disease. Validating process often takes many years to consolidate the
authenticity of a genetic mutation after a disease gene is identified. In the proposed studies, we will take
comprehensive approaches to validating the pathogenic role of TMEM230 mutation in late-onset PD by using
both cell culture and animal models. Upon completion, our study will determine the effect of TMEM230 mutation
on neuronal functions at both systemic and molecular levels.

## Key facts

- **NIH application ID:** 9974760
- **Project number:** 1R01NS115039-01A1
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** xugang xia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,625
- **Award type:** 1
- **Project period:** 2020-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974760

## Citation

> US National Institutes of Health, RePORTER application 9974760, TMEM230 and Neurodegeneration in Parkinson's Disease (1R01NS115039-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9974760. Licensed CC0.

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