· How two sisters’ misfortune led to discovery
· Findings open a new avenue for therapies
· Drugs need to target neuron synapses before neurons degenerate
CHICAGO --- A new Northwestern Medicine study 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% to 2% 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, which will be published Sept. 15 in Neuron, open a new avenue for therapies, the scientists said.
“We showed that dopaminergic synapses become dysfunctional before neuronal death occurs,” said lead author Dr. Dimitri Krainc, chair of neurology at Northwestern University Feinberg School of Medicine and 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, research assistant professor in Krainc’s lab. Other authors are Wesley Peng, Zhong Xie, Daniel Ysselstein, Talia Krainc, Yvette Wong, Niccolò Mencacci, Jeffrey Savas, and D. James Surmeier from Northwestern and Kalle Gehring from McGill University.
The title of the article is “Parkinson’s disease linked parkin mutation disrupts recycling of synaptic vesicles in human dopaminergic neurons.”
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.
Monkeypox (mpox) is a zoonotic disease caused by the mpox virus (MPXV) that has been primarily limited to Central and West African nations since its discovery. The recent spread of the West African lineage of MPXV in historically unaffected countries has raised concerns for global public health. Despite a significant decrease in global mpox cases, there is still a risk of a global resurgence. This study reports the first local case of mpox caused by an imported case in the Chinese mainland. Polymerase chain reaction (PCR) diagnosed the two ...
Announcing a new article publication for Zoonoses journal. Members of the genus, Klebsiella, are becoming increasingly challenging to control due to the recent convergence of multidrug resistant (MDR) and hypervirulent (hv) phenotypes in some species of concern to One Health .
This article provides an introduction to this bacterial genus in the hospital and other settings, update Klebsiella taxonomy, and comment on recent findings describing the prevalence of Klebsiella species in the food chain, a hitherto infrequently recognised ecologic niche. The paper also ...
Customers showing up even when they were sick, not agreeing with the restrictions, and many new tasks for staff. These are factors that contributed to heavier workloads and tougher work environments in pharmacies during the pandemic, a study reveals.
The scientific study, published in the journal Exploratory Research in Clinical and Social Pharmacy, was conducted by researchers at the University of Gothenburg and Åbo Akademi University.
The data consists of a questionnaire that was distributed to all ...
Home-delivery services perpetually compete for the consumer’s attention not only through advertisements but also through methods that reduce basket decision time or make new suggestions. Current research on the topic focuses on optimizing delivery schedules and minimizing costs. However, neither the insufficiency of home delivery options for some cities nor the bigger problem of high carbon emissions due to the abundance of it, are resolved.
A new study conducted by Koç University Industrial Engineering Department professor Barış Yıldız takes a fresh perspective ...
About The Study: Receiving at least two doses of wild-type BNT162b2 vaccine (Pfizer) was associated with a reduced risk of COVID-19 emergency department or urgent care and outpatient visits in children younger than five years. The risk of SARS-CoV-2 encounters appeared lower for those with two versus three doses of BNT162b2, albeit with wide CIs, which is likely due to more immune-evasive Omicron sublineages (e.g., BQ.1-related and XBB-related strains) becoming dominant by the time young children received their third dose and longer median time since dose three compared with dose two.
Authors: Sara Y. Tartof, Ph.D., M.P.H., of ...
New analysis of pilot studies on night shift naps conducted from 2012 to 2018 revealed the ideal snoozing strategy that might help counteract drowsiness and fatigue during a 16-hour overnight duty. The findings can also benefit new parents.
Reanalysis of data showed that when staying up all night, scheduling two nap sessions — a 90-minute one followed by a quick 30-minute shut-eye later — is the optimal choice over a single 120-minute snooze in putting off drowsiness and fatigue. The study was published in the journal Scientific Reports.
“A 90-minute nap to maintain long-term performance and a ...
CHICAGO — Anesthesiology researchers are responsible for some of medicine’s most significant advances, from the Apgar score that tests a newborn’s health to cardiopulmonary resuscitation (CPR). But the number of medical residents in the anesthesiology physician-scientist (researcher) pipeline trails other specialties, particularly among women, according to findings of the Anesthesia Research Council (ARC), published in the journal Anesthesia & Analgesia.
Out of eleven medical specialties, anesthesiology ranked eighth both for the percentage of entering residents ...
PHILADELPHIA—For his work discovering the basis for hemoglobin gene switching and applying those insights to develop a therapy for sickle cell disease and other blood diseases, the Institute for Regenerative Medicine at the University of Pennsylvania awarded Stuart Orkin, MD the third Elaine Redding Brinster Prize in Science or Medicine.
Orkin’s research advanced the understanding of how the fetal hemoglobin gene— the main oxygen carrier protein in the human fetus—is silenced in adults. He also developed a therapy that re-activates the fetal gene for adult hemoglobin gene defects, which cause ...
CORNING, N.Y. | Corning Incorporated | September 15, 2023 - Corning Incorporated (NYSE: GLW) today announced the launch of Corning® Videodrop, an optical technology that applies the principles of interferometric microscopy to quantify the size and concentration of nanoparticles. The latest addition to the company’s growing suite of bioprocessing technology, Videodrop can analyze a solution in less than 60 seconds, and requires only a single 5-10 µl drop of sample material for testing.
The technology is capable of collecting a physical titer of viral vectors such as lentivirus, ...
Soft inflatable robots have emerged as a promising paradigm for applications that require inherent safety and adaptability. However, the integration of sensing and control systems in these robots has posed significant challenges without compromising their softness, form factor, or capabilities. Addressing this obstacle, a research team jointly led by Professor Jiyun Kim (Department of New Material Engineering, UNIST) and Professor Jonbum Bae (Department of Mechanical Engineering, UNIST) has developed groundbreaking “soft valve” technology—an all-in-one solution that integrates sensors and control valves while maintaining complete softness.