Parkinson's disease: a new target
Key to neurodegeneration in Parkinson's disease found
LifeSciencesToday based on University of Pittsburgh School of Medicine: Pitt Researchers Find Key to Parkinson's Disease Neurodegeneration
Scientists from the University of Pittsburgh School of Medicine have identified the main cause of toxicity for brain neurons of the alpha-synuclein protein. Alpha-synuclein is the main component of Levi's bodies, which are considered a characteristic sign of Parkinson's disease. This discovery may help in the development of new treatments for this severe neurodegenerative disease that can slow or stop its development. An article about the study was published in Science Translational Medicine (Maio et al., α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinsons disease).
Parkinson's disease is a neurological disease with characteristic symptoms in the form of tremor, slowness of movements and impaired coordination, which affects about 1 million people in the United States alone. These symptoms are explained by degeneration and loss of neurons in the brain, in particular, which are essential for the initiation and coordination of movements.
"We are very pleased that we have found a mechanism that can be targeted by new treatments for this severe disease," says the head of the study, Professor of neurology Timothy Greenamyre, MD, PhD, director of the Pittsburgh Institute for Neurodegenerative Diseases (Pittsburgh Institute for Neurodegenerative Diseases, PIND).
Modern methods of treating Parkinson's disease can alleviate the symptoms of the disease, but they cannot slow down its inevitable progression. To slow down or stop the development of the disease, scientists must first determine why and how the loss of neurons occurs.
Degenerating neurons contain large accumulations of the alpha-synuclein protein. Since this protein is toxic, individuals whose cells synthesize too much alpha-synuclein or its mutant form are at increased risk of developing Parkinson's disease. In addition, accumulations of alpha-synuclein produce a toxic effect due to disruption of the normal function of mitochondria – organelles responsible for energy production.
To show exactly how alpha-synuclein disrupts mitochondrial function, Professor Greenamire and his group used a well-studied animal model of Parkinson's disease in their new study. The researchers found that by interacting with one of the mitochondrial proteins (TOM20), alpha-synuclein disrupts the optimal functioning of mitochondria, which leads to the production of less energy and the formation of more cell-damaging waste.
Ultimately, the interaction of alpha-synuclein with the TOM2 protein leads to neurodegeneration, explains Professor Greenamire.
The researchers confirmed their results obtained in animal models on the brain tissue of patients with Parkinson's disease.
"The effect of alpha-synuclein on mitochondria is like making a very good coal–fired power plant extremely inefficient, such that not only could it not generate enough electricity, but it would also generate too much toxic pollution," Greenamire continues.
Working with cell cultures, the researchers found two ways to prevent the toxicity of alpha-synuclein: gene therapy, which caused neurons to synthesize more TOM20 protein, protected them from alpha-synuclein; a protein capable of interfering with the interaction of alpha-synuclein with TOM20, prevented the harmful effect of alpha-synuclein on mitochondria.
Although further research is needed to understand whether these approaches will help patients with Parkinson's disease, Professor Greenamire is confident that it makes sense to test one or both of them in clinical trials in an attempt to slow down or stop the otherwise inevitable progression of Parkinson's disease.
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15.06.2016