# Dendrite regulation by the mitochondrial kinase PINK1: Implications for PD/LBD

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $456,100

## Abstract

Dendrite regulation by the mitochondrial kinase PINK1: Implications for PD/LBD
PROJECT SUMMARY.
Synaptic loss is a major structural correlate of dementia, and reduced spine density is observed in the
Parkinson's disease (PD)-Lewy body dementia (LBD) disease spectrum. Autosomal recessive mutations in
PTEN-induced kinase 1 (PINK1) cause early-onset PD and PD with dementia (PDD). Heterozygous carriers
also exhibit cognitive-executive dysfunction and limbic-cortical degeneration. As PINK1 is neuroprotective in
a wide range of genetic and toxin-based models of neurodegeneration, studying its function in neurons may
offer insights into potential therapeutic strategies. Endogenous PINK1 exists in both mitochondrial and
cytosolic compartments. Our prior studies show that these pools of PINK1 play divergent roles in regulating
mitochondrial fission-fusion, mitophagy, calcium homeostasis and dendritic morphogenesis. Moreover, loss
of PINK1 results in dendritic simplification in cortical and midbrain neurons. We hypothesize that PINK1
interacts with cytosolic targets to regulate neuron differentiation and synaptodendritic complexity.
Using mass spectrometry, we identified novel PINK1-interacting proteins, which preliminary studies
implicate in neurite extension or neuronal transport. We will study the role of these novel PINK1 interactions
in regulating dendritogenesis and mitochondrial transport into dendrites using primary cortical and midbrain
neurons, differentiated neuronal cell lines and PINK1 knockout and control mice. The potential role of
phosphorylation and the impact of PD-linked mutations on these neuron-specialized functions of PINK1 will
be analyzed. The neuroprotective potential of upregulating downstream pathway components will be tested
in vitro and in Pink1-/- mice. A better understanding of novel PINK1-driven mechanisms that act to prevent
dendritic simplification may yield valuable insights for neuroprotection in the PD-LBD disease spectrum.

## Key facts

- **NIH application ID:** 9973247
- **Project number:** 5R01NS101628-04
- **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:** $456,100
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973247

## Citation

> US National Institutes of Health, RePORTER application 9973247, Dendrite regulation by the mitochondrial kinase PINK1: Implications for PD/LBD (5R01NS101628-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9973247. Licensed CC0.

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