# Understanding how DOPA decarboxylase modulates tau in disease

> **NIH VA IK2** · VA PUGET SOUND HEALTHCARE SYSTEM · 2022 · —

## Abstract

Background: Neurodegenerative diseases with tau pathology (tauopathies) include Alzheimer's
disease and chronic traumatic encephalopathy. Two major risk factors for developing tauopathies are
aging and repetitive mild traumatic brain injury. The prevalence of tauopathies is expected to rise,
especially among Veterans. However, there are no clinically-approved treatments for tauopathies.
DOPA decarboxylase, the second enzyme in dopamine and serotonin synthesis, was recently
identified as a novel genetic modulator of tauopathy in a Caenorhabditis elegans model. Interestingly,
loss of other enzymes that reduced dopamine and serotonin levels did not affect tauopathy
phenotypes, indicating that changes in dopamine and serotonin precursors, but not dopamine and
serotonin themselves, reduce tauopathy.
Hypothesis: Dopamine and serotonin precursors or their metabolites reduce tauopathy by activating
specific signaling pathways that modulate tau.
Proposed Experiments: The C. elegans tauopathy model and an acute slice ex vivo model of
tauopathy will be used to 1) determine the molecules that mediate the reduction of tauopathy seen
with loss of DOPA decarboxylase 2) identify the signaling pathways that mediate reduction of
tauopathy by loss of DOPA decarboxylase 3) validate mechanisms identified in the C. elegans
tauopathy model with a mammalian tauopathy model.
Expected Outcomes: The proposed studies will result in the identification of novel mechanisms for
regulating tauopathy and new therapeutic strategies for treating tauopathies. Future work will
evaluate the most promising candidates in whole animal models of tauopathy.
Career and Training Goals: My overall career goal is to discover novel therapeutic strategies
against neurodegenerative diseases as head of my own independent research group. The CDA2
goals are therefore 1) to establish an experimental pipeline with animal models for discovery of novel
therapeutics against tauopathies 2) to gain knowledge and experience in various necessary and
relevant skills 3) to establish an independent research laboratory. These goals will be achieved
through various training activities under the guidance from my mentorship team.

## Key facts

- **NIH application ID:** 10438535
- **Project number:** 5IK2BX004341-04
- **Recipient organization:** VA PUGET SOUND HEALTHCARE SYSTEM
- **Principal Investigator:** Rebecca Liang Kow
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438535

## Citation

> US National Institutes of Health, RePORTER application 10438535, Understanding how DOPA decarboxylase modulates tau in disease (5IK2BX004341-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10438535. Licensed CC0.

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