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IN-VIVO MODEL OF PARKINSON’S DISEASE (PD)
Dr. Ronit Sharon: Department of Cell Biochemistry and Human Genetics, Hebrew University-Hadassah School of Medicine, Jerusalem
"Thanks to this BSF grant, we have now established an α-synuclein (α-S) transgenic mouse colony. This funding is helping us with the routine maintenance of the colony and carrying out analyses related to the role of α-S oligomerization in lipid metabolism. "
Prof. Dennis Selkoe: Center for Neurological Diseases, Harvard Medical School, and Brigham and Women's Hospital, Boston
In PD (Parkinson’s disease) and prion diseases, neurons making the neurotransmitter dopamine in the part of the brain controlling muscle movement are impaired or die. Lewy bodies, consisting of potentially neurotoxic abnormally folded α-S (α-synuclein) protein, are the diagnostic hallmark of both these types of NDD (neurodegenerative diseases). Dr. Sharon, who spent many years doing Post-Doctoral research at the Harvard Medical School in Prof. Selkoe’s laboratory before recently returning to Israel to set up her own group at the Hebrew University-Hadassah School of Medicine, originally developed methods for the isolation and analysis of α-S. This research shedding light on the mechanisms underlying PD-like degenerative brain disorders might eventually lead to new types of treatment for these debilitating conditions. Cooperation Dr. Sharon and Prof. Selkoe study the biochemistry, and molecular and cell biology of neuronal degeneration during aging of the mammalian brain. Dr. Selkoe’s laboratory has expertise in β-A aggregation characterizing AD. Dr. Sharon’s group is now using similar methods to study α-S aggregates in PD. As exemplary research in the health sciences, this BSF project was awarded the 2006 Neufeld Memorial Research Award at the recent Annual Dinner. The award will run concurrently with this current BSF grant
Findings Dr. Sharon and Prof. Selkoe focus on the interactions of α-S with PUFAs, and their role in both health and disease. They discovered that α-S interacts with PUFAs, enriching the membranes with these products and, in turn, increasing membrane vesicle trafficking and evoked synaptic vesicle recycling. During long exposure to PUFAs, α-S, normally a monomer (single unit), forms aggregates and Lewy-like bodies in brain neuronal cell lines containing the neurotransmitter DOPA. Other neurotoxic effects were observed (such as the inhibition of mitochondrial complex I).
Lewy-like inclusions (arrows) in dopaminergic cells stained for α-S and ubiquitin show co-localization where they merge. |
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Lewy-Like Inclusions in the PD Mouse Model |
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Lewy-like inclusions (arrows) in dopaminergic cells stained for α-S and ubiquitin show co-localization where they merge. |
