Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Penn Vet Study Reveals a Promising New Target for Parkinson’s Disease Therapies

With a new insight into a model of Parkinson’s disease, researchers from the University of Pennsylvania School of Veterinary Medicine have identified a novel target for mitigating some of the disease’s toll on the brain.
Narayan G. Avadhani, Harriet Ellison Woodward Professor of Biochemistry and chair of the Department of Animal Biology at Penn Vet, was the senior author on the research. Other department members contributing to the work included Prachi Bajpai, Michelle C. Sangar, Shilpee Singh, Weigang Tang, Seema Bansal and Ji-Kang Fang. Co-authors from Vanderbilt University are Goutam Chowdhury, Qian Cheng, Martha V. Martin and F. Peter Guengerich.

To study Parkinson’s, researchers have commonly mimicked the effects of the disease in animals by giving them a compound known as MPTP, a contaminant of the illicit drug MPPP, or synthetic heroin. MPTP causes damage to brain cells that respond to the neurotransmitter dopamine, leading to problems in muscle control, including tremors and difficulty walking.

The common understanding of MPTP’s mechanism was that it entered the brain and was eventually converted to the toxic compound MPP+ by the enzyme MAO-B, which is located on the mitochondria of non-dopaminergic (or dopamine-sensitive) neurons. Scientists believed MPP+ was carried by the action of specific transporters into dopaminergic neurons, where it inhibited mitochondrial function and led to cell death.

In the new study, published in the Journal of Biological Chemistry, the Penn-led team turned its attention to yet another molecule, known as mitochondrial CYP2D6, which until recently has been largely uninvestigated. Previous studies in the investigators’ laboratory showed that CYP2D6, a protein that is predominantly localized to cells’ endoplasmic reticulum, was also targeted to their mitochondria.

Unlike MAO-B, the endoplasmic reticulum-associated CYP2D6 was thought to have a protective effect against MPTP toxicity. The authors now show that mitochondrial CYP2D6 can effectively metabolize MPTP to toxic MPP+, indicating a possible connection between mitochondrial CYP2D6 and Parkinson’s.

“About 80 percent of the human population has only one copy of CYP2D6, but the other 20 percent has variant forms of it and some populations have multiple copies,” Avadhani said. “In those people, the activity of mitochondrial CYP2D6 can be high, and there have been correlations between these variants and the incidence of Parkinson’s disease.”

Working with primary neuronal cells in culture, the researchers showed that mitochondrial CYP2D6 could actively oxidize MPTP to MPP+. When they introduced compounds that selectively inhibited the activity of CYP2D6, this conversion process was largely halted. Neuronal degeneration was also greatly reduced.

“If we add MPTP to dopamine-sensitive neurons and also add a CYP2D6 inhibitor, we see marked protection of the neuronal function,” Avadhani said. “We believe this is a paradigm shift in how we think about the mechanism of Parkinson’s.”

A number of MAO-B inhibitors used in the clinical setting for treating Parkinson’s disease have unwanted side effects. A mitochondrial CYP2D6 inhibitor represents a much more specific and direct target and may thus cause fewer troublesome side effects.

To take the next step with this finding, Avadhani and his colleagues are developing an animal model and using stem cells to confirm the significance of mitochondrial CYP2D6’s role in the development of Parkinson’s symptoms.

The study was supported by National Institutes of Health and the Harriet Ellison Woodward Endowment.

Katherine Unger Baillie | EurekAlert!
Further information:

More articles from Studies and Analyses:

nachricht Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung

nachricht High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>