Feinberg
Northwestern Medicine | Northwestern University | Faculty Profiles

News Center

  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
    • Podcast
  • Press Release
  • Media Coverage
  • Editor’s Picks
    • COVID-19
    • Cardiology
    • Cancer
    • Neurology and Neuroscience
    • Aging and Longevity
    • Artificial Intelligence in Medicine
  • News Archives
  • About Us
    • Media Contact
    • Share Your News
    • News Feeds
    • Social Media
    • Contact Us
Menu
  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
    • Podcast
  • Press Release
  • Media Coverage
  • Editor’s Picks
    • COVID-19
    • Cardiology
    • Cancer
    • Neurology and Neuroscience
    • Aging and Longevity
    • Artificial Intelligence in Medicine
  • News Archives
  • About Us
    • Media Contact
    • Share Your News
    • News Feeds
    • Social Media
    • Contact Us
Home » Early Synaptic Dysfunction Found in Parkinson’s Disease
Disease Discoveries

Early Synaptic Dysfunction Found in Parkinson’s Disease

By Will DossMay 23, 2018
Share
Facebook Twitter Email
Dimitri-Krainc-Feinberg-250
Dimitri Krainc, MD, PhD, the Aaron Montgomery Ward Professor and chair of The Ken and Ruth Davee Department of Neurology, was senior author of a study published in Proceedings of the National Academy of Sciences of the United States of America.

Northwestern Medicine scientists identified a cellular mechanism that leads to neurodegeneration in patients with Parkinson’s disease, according to a study published in Proceedings of the National Academy of Sciences.

Dimitri Krainc, MD, PhD, chair and Aaron Montgomery Ward Professor of Neurology, was the senior author of the study, which demonstrated a link between defective synaptic vesicle endocytosis and accumulation of toxic oxidized dopamine.

When it accumulates in the brain, oxidized dopamine has been shown to mediate the death of dopamine-containing neurons, causing the common motor symptoms observed in Parkinson’s disease (PD) patients, according to previous research conducted by Krainc and published in Science. While people naturally lose dopamine neurons as they age, patients with PD lose a much larger number of these neurons and the remaining cells are no longer able to compensate for the loss of brain function, leading to disease.

“In our prior work, we found that oxidized dopamine is toxic to neurons,” said Krainc, who is also director of the Center for Neurogenetics. “In this paper, we further explain how such oxidized dopamine is formed in synaptic terminals of neurons from patients with Parkinson’s disease.”

The process begins when a protein called auxilin is dysregulated by another protein, a mutated form of LRRK2. Normally, auxilin regulates the process of synaptic vesicle endocytosis, a mechanism that neurons use to replenish the chemical signals needed to communicate with each other.

control-vs-lrrk2-patient-synapses
LRRK2 patient-derived dopaminergic neurons display synaptic defects. Neurons derived from healthy human controls showed normal synaptic vesicle densities in the synaptic terminal (upper image), whereas LRRK2 patients displayed sparse and enlarged vesicles (asterisks, lower image) indicative of defective synaptic function.

In the current study, scientists found that mutations in LRRK2 lead to dysfunctional auxilin and consequently impaired synaptic vesicle endocytosis. This manifests in inefficient packaging of dopamine into synaptic vesicles and an eventual buildup of dopamine in Parkinson’s neurons.

This pool of “extra” dopamine can be rapidly oxidized and become toxic to dopamine neurons, according to the study.

“These findings suggest that early therapeutic intervention in dysfunctional presynaptic terminals may prevent downstream toxic effects of oxidized dopamine and neurodegeneration in PD,” Krainc said.

In addition, these studies of genetic forms of Parkinson’s disease help identify converging pathways in the pathogenesis of sporadic and familial PD, highlighting the importance of investigating such cellular mechanisms to identify specific targets for therapy.

“This study is another example of how the emergence of genetic causes of Parkinson’s has helped us understand how disease develops and where to focus to identify key pathways and targets for drug development,” Krainc said.

Maria Nguyen, a fifth-year student in the Northwestern University Interdepartmental Neuroscience Program, was the first author of the study.

The study was supported by National Institutes of Health Grants R01 NS076054, R01 NS096240 and 2T32AG020506-16.

Genetics Neurology and Neuroscience Research
Share. Facebook Twitter Email

Related Posts

Hospitals Bound to Patient Safety Rules that Aren’t all Backed by Evidence

Jun 24, 2022

Identifying Protein Interactions that Promote Cancer Growth

Jun 24, 2022

Calcium Channel Blockers May Improve Chemotherapy Response

Jun 21, 2022

Comments are closed.

Latest News

Student Spearheads Ukraine Aid Efforts

Jun 27, 2022

Hospitals Bound to Patient Safety Rules that Aren’t all Backed by Evidence

Jun 24, 2022

Identifying Protein Interactions that Promote Cancer Growth

Jun 24, 2022

Combination Treatment May Improve Quality of Life in Kidney Cancer

Jun 23, 2022

Calcium Channel Blockers May Improve Chemotherapy Response

Jun 21, 2022
  • News Center Home
  • Categories
  • Press Release
  • Media Coverage
  • Editor’s Picks
  • News Archives
  • About Us
Flickr Photos
pride7
pride6
pride5
pride4
pride3
pride2
pride1
20220607_Feinberg Campus_0070
20220607_Feinberg Campus_0066
20220607_Feinberg Campus_0054
Northwestern University 2022. Photo by Jim Prisching
20220607_Feinberg Campus_0077

Northwestern University logo

Northwestern University Feinberg School of Medicine

RSS Facebook Twitter LinkedIn Flickr YouTube Instagram
Copyright © 2022 Northwestern University
  • Contact Northwestern University
  • Disclaimer
  • Campus Emergency Information
  • Policy Statements

Type above and press Enter to search. Press Esc to cancel.