Developing a Drug Screening Platform to Identify Inhibitors for Different Alpha-synuclein Strains
While every person with Parkinson’s disease (PD) experiences unique symptoms and progression, all people with PD have a protein in their brain called alpha-synuclein that is not working like it should. Recent studies have shown that each person with PD may have a unique misfolded version of this protein, which may be related to disease severity.
Currently, there is no treatment for PD targeting alpha-synuclein strains, but Kundlik Gadhave, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, is hoping to change that with his upcoming research.
From his lab at Johns Hopkins University in Baltimore, MD, Dr. Gadhave’s research is dedicated to developing an alpha-synuclein strain screening assay that will help to identify inhibitors for different variants, or strains, of misfolded alpha-synuclein.
With the help of his mentor Xiaobo Mao, PhD, Dr. Gadhave has already identified key inhibitors. Dr. Gadhave will use these inhibitors for screening alpha-synuclein proteins from spinal fluid samples of people with PD.
What are Lewy bodies? Lewy bodies are toxic aggregations, or clumps, of alpha synuclein that affect chemicals in the brain, leading to problems with thinking, movement, behavior and mood.
The identified compounds that bind to misfolded alpha-synuclein may also be able to inhibit the formation of Lewy bodies, which are strongly linked to PD. The second half of Dr. Gadhave’s research will test whether the compounds found to bind specific alpha-synuclein strains can slow PD from advancing. This research could lead to the generation of personalized PD therapies that use inhibitors capable of counteracting a unique alpha-synuclein strain.
Dr. Gadhave believes this research can improve how we treat Parkinson’s. “Completing this research will lead to the development of a new compounds for alpha-synuclein strains, which will benefit the therapeutic development for PD.”
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