University of Pittsburgh Researchers Find Key to Parkinson’s Disease Neurodegeneration

University of Pittsburgh Researchers Find Key to Parkinson’s Disease Neurodegeneration

The American Parkinson Disease Association helps fund research that could lead to new therapies to slow or stop progression of Parkinson’s disease.

New York, NY, June 8, 2016 – The American Parkinson Disease Association is a funding partner in supporting researchers at the University of Pittsburgh School of Medicine who have uncovered a major reason why the Parkinson’s-related protein alpha-synuclein, a major constituent of the Lewy bodies that are the pathological hallmark of Parkinson’s disease, is toxic to neurons in the brain. The finding has the potential to lead to new therapies that could slow or stop progression of the devastating illness. The new research appears online today in Science Translational Medicine.

According to David G. Standaert, M.D., Ph.D., Chair of the APDA Scientific Advisory Board, John N. Whitaker Professor and Chair of Neurology, and Director of the Division of Movement Disorders at the University of Alabama at Birmingham, “This is a very important study. It provides new insight into two of the critical mechanisms in Parkinson disease: aggregation of the protein alpha-synculein and dysfunction of mitochondria, the ‘powerhouse’ of neurons. It opens doors to new kinds of treatments to slow or prevent the disease.”

J. Timothy Greenamyre, MD, PhD

The University of Pittsburgh School of Medicine is one of eight APDA Centers of Advanced Research. Lead investigator J. Timothy Greenamyre, M.D., Ph.D., Love Family Professor of Neurology in Pitt’s School of Medicine and director of the Pittsburgh Institute for Neurodegenerative Diseases (PIND) is also the director of the APDA Advanced Center for Parkinson’s Disease Research at PIND and a member of the APDA Scientific Advisory Board. “It’s really exciting that we have found a mechanism we can target to create new treatments for this devastating disease,” said Dr. Greenamyre. “I’ve been involved in Parkinson’s research for more than 25 years and the further I go along, the more urgency I feel to translate what we’re doing in the laboratory into something that’s going to make a meaningful difference for people affected by Parkinson’s disease. I believe these findings will have a lot of impact in the Parkinson’s research community. We couldn’t have done it without the support of APDA!”

Parkinson’s disease (PD) is a degenerative neurological disease characterized by tremor, slowness, and gait and balance difficulties that affects about 1 million people in the United States. The symptoms are caused by the degeneration and loss of neurons in the brain, particularly those crucial for the initiation and coordination of movement.

PIND’s goal is an integrated, interdisciplinary approach to the study of neurodegenerative diseases and their mechanisms, with the aim of transforming cutting-edge science into novel therapies and diagnostics that directly benefit individuals affected by neurodegenerative diseases.

What researchers do know is that the degenerating neurons contain large clumps of a protein called alpha-synuclein. Researchers found that people whose cells make too much alpha-synuclein, or make a mutated form of the protein, are at high risk of developing Parkinson’s Disease because of the protein’s toxicity. Scientists also demonstrated that the accumulation of alpha-synuclein in Parkinson’s Disease is toxic because it disrupts the normal functioning of mitochondria.

In the new study, Dr. Greenamyre and his team – led by coauthors Roberto Di Maio, Ph.D., and Paul Barrett, Ph.D., both of PIND – used a well-established rodent model of Parkinson’s Disease to show exactly how alpha-synuclein disrupts mitochondrial function. They found that by attaching to a mitochondrial protein called TOM20, alpha-synuclein prevented the mitochondria from functioning optimally, which resulted in the production of less energy and more damaging cellular waste.

“Ultimately, this interaction between alpha-synuclein and TOM20 leads to neurodegeneration,” Dr. Greenamyre explained.

The researchers then confirmed their animal findings in brain tissue from people with PD.

“The effects of alpha-synuclein on mitochondria are like making a perfectly good coal-fueled power plant extremely inefficient, so it not only fails to make enough electricity, but also creates too much toxic pollution,” said Dr. Greenamyre.

Using cell cultures, the research team also found two ways to prevent the toxicity caused by alpha-synuclein – gene therapy that forced the neurons to make more TOM20 protein protected them from the alpha-synuclein, and a protein that was able to prevent alpha-synuclein from sticking to TOM20 prevented alpha-synuclein’s harmful effects on mitochondria.

While more research is needed to determine whether these approaches could help Parkinson’s Disease patients, Dr. Greenamyre is optimistic that one or both may ultimately make it into human clinical trials in an effort to slow or halt the otherwise inevitable progression of PD.

Coauthors of the study are Charleen Chu, M.D., Ph.D., Edward Burton, M.D., Ph.D., Teresa Hastings, Ph.D., Eric Hoffman, Ph.D., Caitlyn Barrett, Ph.D., Alevtina Zharikov, Ph.D., Anupom Borah, Ph.D., Xiaoping Hu, B.S., and Jennifer McCoy, B.S., all of PIND.

APDA is proud to have been one of the funders of this collaborative effort. Additional research grants were awarded from the DSF Charitable Foundation, the Ri.MED Foundation, the Consolidated Anti-Aging Foundation, the National Institutes of Health (grants NS095387, NS059806, ES022644, ES020718, ES020327, NS065789, AG026389 and P50AG005133), the United States Department of Veterans’ Affairs (grant 1I01BX000548), the Blechman Foundation, and the Department of Biotechnology, Government of India.

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About The American Parkinson Disease Association (APDA)
APDA was founded in 1961 with the dual purpose to Ease the Burden – Find the Cure for Parkinson’s disease. In that time, APDA has raised and invested more than $89 million to fund research, patient services and education, and elevate public awareness. As the country’s largest Parkinson’s grassroots organization, APDA aims to Ease the Burden for the more than one million Americans with Parkinson’s disease and their families through a nationwide network of Chapters, Information and Referral (I&R) Centers, and support groups. APDA pursues its efforts to Find the Cure by funding Centers for Advanced Research and awarding grants to fund the most promising research toward discovering the cause(s) and finding the cure for Parkinson’s disease.

About the University of Pittsburgh School of Medicine
As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see