Related Experiment Video

Updated: Jun 12, 2025

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
08:55

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

Published on: December 14, 2017

15.0K

A new LRRK2 variant in a family with Parkinson's disease affects binding to RAB8A

Lydia Vela-Desojo1, Alba Pascual2,3, Victor Montal4

  • 1Movement Disorders Unit, Department of Neurology, Hospital Universitario Fundación Alcorcón, Madrid, Spain.

NPJ Parkinson'S Disease
|June 7, 2025
PubMed

Insights

A novel LRRK2 gene variant, p.[Leu119Pro;Leu488Pro], located in the ARM domain, is linked to familial Parkinson's disease (PD). This variant alters protein interactions and may cause PD by affecting LRRK2's function.

Area of Science:

  • Neurogenetics
  • Molecular Biology
  • Pathology

Background:

  • Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are a common genetic cause of Parkinson's disease (PD).
  • LRRK2 variants affecting the armadillo (ARM) domain may indirectly influence protein activity through interactions with RAB proteins.

Purpose of the Study:

  • To investigate a novel LRRK2 gene variant, p.[Leu119Pro;Leu488Pro], identified in a family with recurrent Parkinson's disease.
  • To elucidate the molecular mechanisms by which this ARM domain variant contributes to PD pathogenesis.

Main Methods:

  • Clinical examination of nine family members.
  • Neuropathological analysis of the index case.
  • In silico analysis, functional genomics with recombinant LRRK2, and molecular docking studies.

Main Results:

  • The p.[Leu119Pro;Leu488Pro] variant was identified in a family with PD.
  • In silico analysis predicted structural and binding alterations.
  • Functional studies showed increased interaction and binding affinity of LRRK2^Leu119Pro;Leu488Pro with RAB8A.

Conclusions:

  • The novel LRRK2 variant p.[Leu119Pro;Leu488Pro] is proposed as a cause of familial Parkinson's disease.
  • The variant's effects on LRRK2-RAB protein interactions suggest a novel mechanism in PD pathogenesis.

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
Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation12:49

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation

Published on: March 21, 2020

7.4K

Related Concept Videos

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.
39.2K
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...
492
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...
233
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.9K