# Neuronal quality control and neuroprotection in tauopathies

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $504,368

## Abstract

Dendritic simplification and synaptic loss represent major structural correlates of dementia in Alzheimer’s
disease (AD) and frontotemporal dementia (FTD). Mutations in the microtubule-associated protein tau are a
major cause of FTD and increase the risk of developing AD. Mutations in valosin-containing protein (VCP)
have also been linked to familial FTD. In the prior project period, we discovered that dendritic calcium
dyshomeostasis, dysregulated mitophagy and altered protein phosphorylation contribute to dendritic
shrinkage in several models of neurodegeneration. We also discovered a novel interaction between VCP and
the neuroprotective kinase PTEN-induced kinase 1 (PINK1). VCP is a multifunctional protein implicated in
protein degradation, vesicular transport and Golgi remodeling, and these functions are mediated by distinct
VCP cofactors. Based on preliminary data, we hypothesize that PINK1 interacts with VCP to prevent tau-
mediated dendritic shrinkage. We will utilize primary rodent cortical neurons and human iPSC-derived
neurons to study quality control mechanisms that contribute to neuroprotection against tau-mediated
degeneration of dendritic arbors and spines. We will also assess the neuroprotective potential of upregulating
PINK1 signaling in vitro and in vivo. Completion of these studies will reveal how proteins implicated in different
neurodegenerative diseases function together to protect against tau-mediated neurodegeneration.

## Key facts

- **NIH application ID:** 10056240
- **Project number:** 2R01AG026389-11A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Charleen T Chu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,368
- **Award type:** 2
- **Project period:** 2007-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056240

## Citation

> US National Institutes of Health, RePORTER application 10056240, Neuronal quality control and neuroprotection in tauopathies (2R01AG026389-11A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10056240. Licensed CC0.

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