Related Experiment Video

Updated: Dec 6, 2025

Generation of Induced Neural Stem Cells from Peripheral Mononuclear Cells and Differentiation Toward Dopaminergic Neuron Precursors for Transplantation Studies
12:13

Generation of Induced Neural Stem Cells from Peripheral Mononuclear Cells and Differentiation Toward Dopaminergic Neuron Precursors for Transplantation Studies

Published on: July 11, 2019

7.5K

Endosomal dysfunction in iPSC-derived neural cells from Parkinson's disease patients with VPS35 D620N

Keiko Bono1,2, Chikako Hara-Miyauchi1, Shunsuke Sumi1

  • 1Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

Molecular Brain
|October 9, 2020
PubMed

Insights

Mutations in the Vacuolar protein sorting 35 (VPS35) gene cause Parkinson's disease (PD) by impairing endosomal trafficking and leading to neuronal cell death and alpha-synuclein accumulation.

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Vacuolar protein sorting 35 (VPS35) mutations are linked to familial Parkinson's disease (PD), designated PARK17.
  • VPS35 is crucial for the retromer complex, essential for endosomal trafficking.
  • The precise role of VPS35 dysfunction in PD pathogenesis remains to be fully elucidated.

Purpose of the Study:

  • To investigate the cellular mechanisms underlying PD in patients with the VPS35 D620N mutation.
  • To analyze neuronal and glial cells derived from patient-specific induced pluripotent stem cells (iPSCs).

Main Methods:

  • Utilized human induced pluripotent stem cell (iPSC)-derived neurons and glial cells from PD patients carrying the VPS35 D620N mutation.
  • Assessed dopaminergic (DA) neuron viability, endosomal trafficking dynamics (Rab5a, Rab7a), and vesicle localization.
  • Investigated alpha-synuclein aggregation in DA neurons.

Main Results:

  • PD patient-derived neurons exhibited significant apoptotic cell death.
  • Endosomal trafficking was impaired, characterized by slower movement and reduced fission/fusion of Rab5a/Rab7a-positive endosomes.
  • Abnormal retromer-dependent vesicle localization was observed in glial cells, and alpha-synuclein accumulated in TH-positive DA neurons.

Conclusions:

  • VPS35 D620N mutation induces dopaminergic neuron death, endosomal dysfunction, and alpha-synuclein accumulation.
  • Patient-derived iPSCs offer a valuable model for studying PARK17-associated PD pathophysiology.
  • This study highlights the critical role of VPS35 in maintaining neuronal health and endosomal integrity in Parkinson's disease.
Keywords:
EndosomesParkinson’s diseaseRetromerVPS35iPSC

More Related Videos

Author Spotlight: Generating Neuronal Phenotypic Profiles - A Protocol to Culture and Image Human Midbrain Dopaminergic Neurons09:21

Author Spotlight: Generating Neuronal Phenotypic Profiles - A Protocol to Culture and Image Human Midbrain Dopaminergic Neurons

Published on: July 7, 2023

1.9K
The Use of Primary Human Fibroblasts for Monitoring Mitochondrial Phenotypes in the Field of Parkinson's Disease15:09

The Use of Primary Human Fibroblasts for Monitoring Mitochondrial Phenotypes in the Field of Parkinson's Disease

Published on: October 3, 2012

17.2K

Related Concept Videos

EPS and iPS Cells in Disease Research01:21

EPS and iPS Cells in Disease Research

Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
3.2K
iPS Cell Differentiation01:22

iPS Cell Differentiation

The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
3.0K
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
4.3K
Parkinson's Disease: Overview01:15

Parkinson's Disease: Overview

Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
1.5K
Neural Regulation01:37

Neural Regulation

Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
42.6K