Feinberg
Northwestern Medicine | Northwestern University | Faculty Profiles

News Center

  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
  • Press Releases
  • Media Coverage
  • Podcasts
  • 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
  • Press Releases
  • Media Coverage
  • Podcasts
  • 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 » Newly Discovered Trigger of Parkinson’s Upends Common Beliefs
Disease Discoveries

Newly Discovered Trigger of Parkinson’s Upends Common Beliefs

By Marla PaulSep 18, 2023
Share
Facebook Twitter Email

Damage starts much earlier than the death of dopamine neurons, scientists report

Dimitri Krainc headshot
Senior author Dimitri Krainc, MD, chair of Neurology and director of the Simpson Querrey Center for Neurogenetics.

A new Northwestern Medicine study published in the journal Neuron challenges a common belief in what triggers Parkinson’s disease.

Degeneration of dopaminergic neurons is widely accepted as the first event that leads to Parkinson’s. But the new study suggests that a dysfunction in the neuron’s synapses — the tiny gap across which a neuron can send an impulse to another neuron — leads to deficits in dopamine and precedes the neurodegeneration.

Parkinson’s disease affects 1 percent to 2 percent of the population and is characterized by resting tremor, rigidity and bradykinesia (slowness of movement). These motor symptoms are due to the progressive loss of dopaminergic neurons in the midbrain.

The findings open a new avenue for therapies, the scientists said.

“We showed that dopaminergic synapses become dysfunctional before neuronal death occurs,” said senior author Dimitri Krainc, MD, chair of Neurology director of the Simpson Querrey Center for Neurogenetics. “Based on these findings, we hypothesize that targeting dysfunctional synapses before the neurons are degenerated may represent a better therapeutic strategy.”

The study investigated patient-derived midbrain neurons, which is critical because mouse and human dopamine neurons have a different physiology and findings in the mouse neurons are not translatable to humans, as highlighted in Krainc’s research recently published in Science.

Northwestern scientists found that dopaminergic synapses are not functioning correctly in various genetic forms of Parkinson’s disease. This work, together with other recent studies by Krainc’s lab, addresses one of the major gaps in the field: how different genes linked to Parkinson’s lead to degeneration of human dopaminergic neurons.

Neuronal recycling plant

Imagine two workers in a neuronal recycling plant. It’s their job to recycle mitochondria, the energy producers of the cell, that are too old or overworked. If the dysfunctional mitochondria remain in the cell, they can cause cellular dysfunction. The process of recycling or removing these old mitochondria is called mitophagy. The two workers in this recycling process are the genes Parkin and PINK1. In a normal situation, PINK1 activates Parkin to move the old mitochondria into the path to be recycled or disposed of.

It has been well-established that people who carry mutations in both copies of either PINK1 or Parkin develop Parkinson’s disease because of ineffective mitophagy.

The story of two sisters whose disease helped advance Parkinson’s research

Two sisters had the misfortune of being born without the PINK1 gene, because their parents were each missing a copy of the critical gene. This put the sisters at high risk for Parkinson’s disease, but one sister was diagnosed at age 16, while the other was not diagnosed until she was 48.

The reason for the disparity led to an important new discovery by Krainc and his group. The sister who was diagnosed at 16 also had partial loss of Parkin, which, by itself, should not cause Parkinson’s.  

“There must be a complete loss of Parkin to cause Parkinson’s disease. So, why did the sister with only a partial loss of Parkin get the disease more than 30 years earlier?” Krainc asked.

As a result, the scientists realized that Parkin has another important job that had previously been unknown. The gene also functions in a different pathway in the synaptic terminal — unrelated to its recycling work— where it controls dopamine release. With this new understanding of what went wrong for the sister, Northwestern scientists saw a new opportunity to boost Parkin and the potential to prevent the degeneration of dopamine neurons.

“We discovered a new mechanism to activate Parkin in patient neurons,” Krainc said. “Now, we need to develop drugs that stimulate this pathway, correct synaptic dysfunction and hopefully prevent neuronal degeneration in Parkinson’s.”

The first author of the study is Pingping Song, PhD, research assistant professor of Neurology in the Division of Movement Disorders. Other Northwestern co-authors were Wesley Peng, MD, PhD; Zhong Xie, PhD, research assistant professor of Neuroscience; Daniel Ysselstein, PhD; Talia Krainc; Yvette Wong, PhD, assistant professor of Neurology in the Division of Movement Disorders; Niccolò Mencacci, MD, PhD, assistant professor of Neurology in the Division of Movement Disorders; Jeffrey Savas, PhD, assistant professor of Neurology in the Division of Behavioral Neurology; and D. James Surmeier, PhD, the chair and Nathan Smith Davis Professor of Neuroscience. Kalle Gehring, PhD, from McGill University was also a co-author.

This work was supported by National Institutes of Health grants R01NS076054, R3710 NS096241, R35 NS122257 and NS121174, all from the National Institute of Neurological Disorders and Stroke.  

Neurology Neurology and Neuroscience Press Release Research
Share. Facebook Twitter Email

Related Posts

Mapping Neural Activity Patterns and Odor Perception  

Sep 28, 2023

Small, Implantable Device Could Sense and Treat Cancer

Sep 26, 2023

Gene Linked to Glioblastoma Stem Cell Self-Renewal and Immunosuppression

Sep 26, 2023

Comments are closed.

Latest News

Mapping Neural Activity Patterns and Odor Perception  

Sep 28, 2023

Lloyd-Jones Announces He is Stepping Down as Chair of Preventive Medicine

Sep 27, 2023

Small, Implantable Device Could Sense and Treat Cancer

Sep 26, 2023

Gene Linked to Glioblastoma Stem Cell Self-Renewal and Immunosuppression

Sep 26, 2023

Northwestern Simulation’s In Situ Training Tests Cardiac Arrest Response Teams

Sep 25, 2023
  • News Center Home
  • Categories
  • Press Release
  • Media Coverage
  • Editor’s Picks
  • News Archives
  • About Us
Flickr Photos
20230914_NM461
20230914_NM644
20230914_NM345
20230914_NM444
20230914_NM464
20230914_NM520
20230914_NM673
20230914_NM641
20230914_NM612
20230914_NM608
20230914_NM602
20230914_NM597

Northwestern University logo

Northwestern University Feinberg School of Medicine

RSS Facebook Twitter LinkedIn Flickr YouTube Instagram
Copyright © 2023 Northwestern University
  • Contact Northwestern University
  • Disclaimer
  • Campus Emergency Information
  • Policy Statements

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