# Functions of parkin in Parkinson’s disease

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $450,326

## Abstract

Summary
 Nigral dopaminergic (DA) neurons (i.e. A9 DA neurons) that are lost in Parkinson’s
disease (PD) have autonomous pacemaking action potentials, massive axon arborization, and
expression of GIRK2, but not calbindin. Despite the significant progress in the differentiation of
human embryonic stem cells (hESCs) to midbrain DA neurons, it has been difficult to generate
A9 type DA neurons, particularly from human induced pluripotent stem cells (iPSCs). We
developed an improved floorplate-based method to differentiate patient-specific iPSCs to
midbrain DA neurons that expressed appropriate markers for A9 type cells and exhibited
calcium channel-dependent autonomous pacemaking activities independent of glutamatergic
inputs. These iPSC-derived DA neurons extended elaborate neuronal fibers when grafted to 6-
OHDA-lesioned rats and restored locomotor deficits. We have generated isogenic pairs of
iPSCs by repairing parkin mutations in patient cells and by introducing parkin mutations to
control cells. Using these isogenic iPSCs, we will study how parkin mutations mechanistically
disrupt the precision of dopaminergic transmission in three different preparations: monolayer
cultures, brain organoids, and graft in 6-OHDA-lesioned rat brains. The three novel approaches
will enable us to approximate the situation in the brains of PD patients. The study will bridge the
gap between mechanistic understanding of the cellular function of parkin and its role in PD
pathophysiology that is directly linked to the motor symptoms. The results will stimulate the
development of disease-modifying therapies of Parkinson's disease .

## Key facts

- **NIH application ID:** 9894863
- **Project number:** 5R01NS102148-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** JIAN FENG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,326
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894863

## Citation

> US National Institutes of Health, RePORTER application 9894863, Functions of parkin in Parkinson’s disease (5R01NS102148-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9894863. Licensed CC0.

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