Related Experiment Video

Updated: Jun 4, 2025

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models
13:47

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models

Published on: March 29, 2019

9.5K

α-Synuclein Gene Hypomethylation in LRRK2 Parkinson's Disease Patients

Lorena de Mena1,2, Guillem Parés1,2, Alicia Garrido2,3,4

  • 1Laboratory of Parkinson's and Other Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.

Movement Disorders : Official Journal of the Movement Disorder Society
|December 23, 2024
PubMed
Abstract

Insights

Leucine-rich repeat kinase 2 (LRRK2)-driven Parkinson's disease (L2PD) shows α-Synuclein (SNCA) gene hypomethylation, similar to idiopathic Parkinson's disease. This epigenetic change in SNCA is a novel finding in L2PD patients.

Area of Science:

  • Neuroscience
  • Genetics
  • Epigenetics

Background:

  • Idiopathic Parkinson's disease (iPD) is associated with α-Synuclein (SNCA) gene hypomethylation.
  • Leucine-rich repeat kinase 2 (LRRK2)-driven Parkinson's disease (L2PD) shares clinical similarities with iPD.
  • Investigating SNCA epigenetic status in LRRK2 cohorts is crucial due to clinical resemblances.

Purpose of the Study:

  • To investigate the epigenetic status of the SNCA gene in a Spanish cohort of LRRK2 mutation carriers.
  • To compare SNCA methylation patterns between L2PD patients, nonmanifesting carriers, iPD patients, and healthy controls.

Main Methods:

  • Assessed methylation levels of 23 CpG sites in the SNCA promoter region.
  • Utilized peripheral blood DNA from 475 subjects: 151 L2PD patients, 55 LRRK2 nonmanifesting carriers, 115 iPD patients, and 154 healthy controls.
  • Employed quantitative methylation analysis techniques.

Main Results:

  • Significant SNCA hypomethylation observed in 11 of 23 CpGs (48%) in L2PD patients compared to controls.
  • Extensive SNCA hypomethylation found in 22 of 23 CpGs (96%) in iPD patients.
  • Asymptomatic LRRK2 mutation carriers exhibited SNCA methylation profiles similar to healthy controls.

Conclusions:

  • This study provides the first evidence of SNCA hypomethylation in L2PD patients.
  • SNCA hypomethylation is a potential epigenetic biomarker in LRRK2-driven Parkinson's disease.
  • Further validation in diverse global LRRK2 cohorts is recommended to confirm these findings.
Keywords:
LRRK2Parkinson'sSNCAepigeneticsleucine‐rich repeat kinase 2promoterα‐Synuclein

More Related Videos

Assaying the Kinase Activity of LRRK2 in vitro06:09

Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

22.5K
Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag08:55

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

14.9K

Related Concept Videos

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.
39.1K
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
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...
476
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...
216