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Related Concept Videos

Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
Parkinson Disease l: Introduction01:24

Parkinson Disease l: Introduction

Parkinson’s disease is a chronic, progressive neurodegenerative disorder that primarily affects movement. It is characterized by motor symptoms such as resting tremors, muscle rigidity, bradykinesia (slowness of movement), and postural instability. Patients may notice hand tremors at rest, stiffness during movement, or a shuffling gait. In addition to motor features, non-motor symptoms include sleep disturbances, mood and behavioral changes, constipation, and cognitive impairment, all of which...
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 to...
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 its...
Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
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,...

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Related Experiment Video

Updated: May 31, 2026

Gait Analysis of Age-dependent Motor Impairments in Mice with Neurodegeneration
07:46

Gait Analysis of Age-dependent Motor Impairments in Mice with Neurodegeneration

Published on: June 18, 2018

VPS35 mutations in Parkinson disease.

Carles Vilariño-Güell1, Christian Wider, Owen A Ross

  • 1Department of Medical Genetics, University of British Columbia, Vancouver, Canada. carles@can.ubc.ca

American Journal of Human Genetics
|July 19, 2011
PubMed
Summary

A novel mutation in the vacuolar protein sorting 35 (VPS35) gene is identified as a cause of autosomal-dominant Parkinson disease (PD). This finding implicates VPS35 in neurodegeneration and Parkinson disease pathogenesis.

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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

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Last Updated: May 31, 2026

Gait Analysis of Age-dependent Motor Impairments in Mice with Neurodegeneration
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Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation
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Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation

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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Area of Science:

  • Genetics
  • Neuroscience
  • Molecular Biology

Background:

  • Mendelian disorders are typically identified through family studies, linkage analysis, and candidate gene sequencing.
  • Parkinson disease (PD) is a complex neurodegenerative disorder with a significant genetic component.

Purpose of the Study:

  • To investigate the genetic cause of autosomal-dominant, late-onset Parkinson disease in a Swiss kindred using next-generation sequencing.
  • To identify the specific genetic mutation responsible for the observed Parkinson disease phenotype.

Main Methods:

  • Whole exome sequencing was performed on affected individuals from a Swiss family with Parkinson disease.
  • Mutation analysis was conducted, including segregation analysis within the family and screening in control populations.
  • Further sequencing was performed on additional familial PD cases to identify other potential variants.

Main Results:

  • A novel mutation, VPS35 c.1858G>A (p.Asp620Asn), in the vacuolar protein sorting 35 (VPS35) gene was identified as the likely cause of Parkinson disease in the Swiss kindred.
  • This mutation was present in all affected family members and in additional patients with sporadic PD, but absent in 3,309 controls.
  • Another VPS35 missense variant (c.946C>T; p.Pro316Ser) was found in one pedigree, but its pathogenicity remains uncertain.

Conclusions:

  • Disruption of VPS35 function, a key component of the retromer complex involved in protein trafficking, is implicated in the pathogenesis of Parkinson disease.
  • This study highlights the role of VPS35 in endosome-trans-Golgi trafficking and membrane-protein recycling in the context of neurodegeneration.
  • The findings expand our understanding of the genetic underpinnings of Parkinson disease and identify VPS35 as a potential therapeutic target.