Research on alpha-synuclein, a lead target for therapy to slow or stop Parkinson’s and potential marker of disease progression, is quickly advancing, and scientists are learning more about this protein’s role in Parkinson’s disease (PD). Recently, researchers discovered how this protein damages neurons in PD, revealing new potential strategies for developing neuroprotective therapies.
A group of researchers led by J. Timothy Greenamyre, MD, PhD, director of the Pittsburgh Institute for Neurodegenerative Diseases (PIND), studied the interaction between alpha-synuclein and mitochondria using pre-clinical models of Parkinson’s.
Previous studies showed that mitochondria, mini “powerhouses” in the cell that produce energy, are dysfunctional in PD and may be related to alpha-synuclein. However, their direct interaction was not well understood until now.
The researchers found that certain types of the alpha-synuclein protein bind to mitochondria and impair energy production in dopamine neurons, as reported in Science Translational Medicine. Dr. Greenamyre and his colleagues also identified potential ways to prevent toxicity by protecting mitochondria from alpha-synuclein binding using specific proteins. Their results were then confirmed using samples of brain tissue from individuals who had PD.
“These results are very promising for several reasons. First, it identifies a very specific mechanism by which altered forms of alpha-synuclein cause mitochondria in neurons to function sub-optimally. Second, it identifies specific forms of alpha-synuclein that are toxic to mitochondria,” said Dr. Greenamyre, who is also a member of the scientific advisory board at The Michael J. Fox Foundation (MJFF). “In addition, these findings help explain why dopamine neurons are so vulnerable to degeneration in PD.”
Funding studies on alpha-synuclein is a major priority of the MJFF strategy (although the Foundation did not fund this particular study). In addition to funding the development of therapies that target alpha-synuclein, MJFF also support research into the biology of alpha-synuclein and how to measure alpha-synuclein levels. Their most recent effort aims to qualify alpha-synuclein as a biomarker for PD by standardizing the way it is measured.
More research is needed to determine how new therapeutic strategies based on this study could help individuals with PD. “These findings suggest several new approaches to protect neurons from alpha-synuclein toxicity – and these are being tested now in models of PD,” added Dr. Greenamyre.
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