Related Experiment Video

Updated: Jul 12, 2025

Author Spotlight: Establishing a New Fluorescence-Based Protocol for In Vivo Mitochondrial Morphology Analysis in Parkinson's Disease
06:07

Author Spotlight: Establishing a New Fluorescence-Based Protocol for In Vivo Mitochondrial Morphology Analysis in Parkinson's Disease

Published on: June 23, 2023

1.6K

Mitochondrial Dysfunction in Dopaminergic Neurons Derived from Patients with LRRK2- and SNCA-Associated Genetic Forms

Anna S Vetchinova1, Marina R Kapkaeva1, Mikhail V Ivanov2

  • 1Laboratory of Neurobiology and Tissue Engineering, Brain Science Institute, Research Center of Neurology, Moscow 125367, Russia.

Current Issues in Molecular Biology
|October 27, 2023
PubMed

Insights

Genetic mutations in LRRK2 and SNCA genes are linked to Parkinson's disease (PD). Mitochondrial gene activity and structure are altered in PD patient-derived cells, offering potential biomarkers for early diagnosis.

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Parkinson's disease (PD) is a prevalent neurodegenerative disorder with genetic links, particularly mutations in LRRK2 and SNCA genes.
  • Early diagnosis of PD is crucial for developing effective neuroprotective strategies, highlighting the need for reliable biomarkers.
  • Induced pluripotent stem cell (iPSC) technology offers a powerful platform for modeling PD and discovering novel biomarkers in vitro.

Purpose of the Study:

  • To investigate mitochondrial gene expression and ultrastructural changes in iPSC-derived dopaminergic neurons from patients with LRRK2- and SNCA-associated Parkinson's disease.
  • To identify potential mitochondrial biomarkers for early diagnosis and prognosis of Parkinson's disease.

Main Methods:

  • Utilized multiplex gene expression profiling with barcoding on the Nanostring platform to analyze 105 mitochondrial proteome genes.
  • Employed electron microscopy to examine ultrastructural mitochondrial morphology in patient-derived iPSC cultures.
  • Compared gene activity and mitochondrial morphology between iPSC-derived neurons from PD patients (LRRK2 and SNCA mutations) and healthy donors.

Main Results:

  • Electron microscopy revealed ultrastructural mitochondrial abnormalities in both LRRK2 and SNCA mutant cells compared to healthy controls.
  • SNCA-mutant cells showed a significantly reduced ratio of mitochondrial area to total cytoplasm area.
  • Nanostring analysis identified differential gene expression in pathways including respiratory complexes, ATP production, mitochondria-endoplasmic reticulum interactions, mitophagy, calcium regulation, and mitochondrial DNA replication.

Conclusions:

  • Mitochondrial dysfunction is a key feature in genetic forms of Parkinson's disease, evident at both the ultrastructural and gene expression levels.
  • Altered mitochondrial gene activity in iPSC-derived neurons represents a promising avenue for identifying diagnostic and prognostic biomarkers for Parkinson's disease.
  • This study underscores the potential of iPSC technology combined with advanced profiling techniques for understanding PD pathogenesis and biomarker discovery.
Keywords:
LRRK2Parkinson’s diseaseSCNAalpha-synucleindardarindopaminergic neuronsinduced pluripotent stem cellsmitochondriatranscriptomics

More Related Videos

Author Spotlight: Decoding Mitochondrial Aging08:48

Author Spotlight: Decoding Mitochondrial Aging

Published on: June 30, 2023

4.0K
Analyzing Mitochondrial Transport and Morphology in Human Induced Pluripotent Stem Cell-Derived Neurons in Hereditary Spastic Paraplegia07:32

Analyzing Mitochondrial Transport and Morphology in Human Induced Pluripotent Stem Cell-Derived Neurons in Hereditary Spastic Paraplegia

Published on: February 9, 2020

7.8K

Related Concept Videos

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...
567
Parkinson's Disease: Treatment01:24

Parkinson's Disease: Treatment

Neurodegenerative disorders, such as Parkinson's Disease (PD), involve the gradual and irreversible destruction of neurons in particular brain areas. These disorders exhibit standard features like proteinopathies, selective vulnerability of some neurons, and an interaction of intrinsic properties, genetics, and environmental influences in neural injury.
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
281
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,...
3.8K
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.
39.5K