NIEHS-funded researchers find potential treatment for Parkinson’s disease
By Andrew Gould and Joe Balintfy
Blocking a particular mitochondrial fission protein could be an effective treatment to reverse or slow the progression of Parkinson's disease, according to a study in mice led by an NIEHS-funded researcher from Plymouth University in the U.K. The study findings were published Nov. 5 in Nature Communications.
“It’s a promising finding that takes advantage of our new understanding of mitochondria as dynamic networks,” said Cindy Lawler, Ph.D., head of the NIEHS Genes, Environment, and Health Branch. “While much further study is needed before the approach can be translated to potential treatments for human patients with Parkinson’s, demonstrating positive results in an animal model is an important step forward.”
This study shows that the processes of mitochondria could be modified to reduce cell death and deficits in dopamine release involved in Parkinson's.
Understanding Parkinson’s and mitochondrial processes
Mitochondria are small structures within nerve cells that keep the cells healthy and working properly. They undergo frequent changes in shape, size, number, and location, either through mitochondrial fission, which leads to multiple, smaller mitochondria, or through mitochondrial fusion, resulting in larger mitochondria. These processes are controlled mainly by their respective mitochondrial fission and fusion proteins. A balance of mitochondrial fission and fusion is critical to cell function and viability.
Parkinson's is a complex disorder of the central nervous system, and the second most common progressive neurodegenerative disease in the U.S., after Alzheimer’s disease. Parkinson’s progresses slowly, and motor symptoms emerge as small clusters of a specific type of nerve cell in the midbrain die. The gradual loss of these neurons results in reduction of a critical neurotransmitter called dopamine, a chemical responsible for transmitting messages to parts of the brain that coordinate muscle movement. Understanding why these neurons die or do not work properly could lead to new therapies.
Blocking the right protein
The research team found that when a particular mitochondrial fission protein, GTPase dynamin-related protein-1, or Drp1, was blocked, using either gene therapy or a chemical approach in experimental models of Parkinson’s disease in mice, it reduced both cell death and the deficits in dopamine release, effectively reversing the Parkinson’s process. The results suggest that finding a strategy to inhibit Drp1 could be a potential treatment for Parkinson’s, also known as PD.
“Our findings show exciting potential for an effective treatment for PD, and pave the way for future in-depth studies in this field,” said Kim Tieu, Ph.D., team lead at the Plymouth University Peninsula Schools of Medicine and Dentistry. “It’s worth noting that other researchers are also targeting this mitochondrial fission/fusion pathway as potential treatments for other neurological diseases, such as Alzheimer’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis.”
Tieu started this research when he was a lead researcher at the University of Rochester School of Medicine and Dentistry in New York, and continued it after his move to Plymouth University.
For more on this story, read the Plymouth University press release.
Citation: Rappold PM, Cui M, Grima JC, Fan RZ, de Mesy-Bentley KL, Chen L, Zhuang X, Bowers WJ, Tieu K. 2014. Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo. Nat Commun; doi:10.1038/ncomms6244 [Online 5 November 2014].
(Andrew Gould is a public relations specialist for Plymouth University Peninsula Schools of Medicine and Dentistry, and School of Biomedical and Healthcare Sciences. Joe Balintfy is a public affairs specialist in the NIEHS Office of Communications and Public Liaison.)