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

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $573,282

## 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
Alzheimer’s disease (AD) and the Lewy body dementia (LBD) disease spectrum. Autosomal recessive
mutations in PTEN-induced kinase 1 (PINK1) cause early-onset Parkinson’s disease (PD) and PD with
dementia (PDD), with heterozygous carriers exhibiting cognitive-executive dysfunction and cortical
degeneration in the absence of motor symptoms. Given that wild type PINK1 is reduced in the cortex of
patients with sporadic PDD and AD, we studied the role of endogenous PINK1 in regulating dendritic
branching, spine density and function in the previous project period. We elucidated a novel signaling
pathway by which PINK1 promotes dendritic arborization, discovered that Pink1-/- neurons exhibit reduced
dendritic spine density in vitro and in vivo, and identified a novel PINK1-regulated motor protein
phosphorylation site. In the current proposal, we will test the hypothesis that alterations in dendritic
mitochondrial transport in PINK1-deficient neurons result in defective mitochondrial support of
synaptic plasticity. We will employ molecular genetic manipulations, glutamate uncaging and
electrophysiology to study the impact of PINK1 loss-of-function on dendritic transport of mitochondria,
mitochondrial motor proteins, and perisynaptic mitochondrial positioning in Pink1-/- mouse neurons and
PINK1-mutated patient iPSC-derived cortical neurons. We will also study the impact of PINK1 deficiency on
spine dynamics and cognitive function in Pink1-/- mice in vivo. A better understanding of novel PINK1-
driven mechanisms that promote dendritic health and spine function may yield valuable insights relevant to
neuroprotection for these devastating neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10974955
- **Project number:** 2R01NS101628-06
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Charleen T Chu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $573,282
- **Award type:** 2
- **Project period:** 2017-09-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974955

## Citation

> US National Institutes of Health, RePORTER application 10974955, Dendrite regulation by the mitochondrial kinase PINK1: Implications for PD/LBD (2R01NS101628-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10974955. Licensed CC0.

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