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New Cell Model for Parkinsonís Disease
- Nov 04 2011
For the first time, scientists have created a cellular model that simulates the process of nerve cells “infecting” neighboring cells in Parkinson’s. They have shown that small amounts of mis-folded alpha-synuclein protein can enter healthy neurons, where it “seeds” the formation of protein clumps that eventually kill the cells. The study, which was published in the October 6, 2011 issue of Neuron, may provide new insights into how Parkinson’s and other neurodegenerative diseases progress.
While it is well known that Parkinson’s is a progressive disease, the mechanisms by which the disease progresses are unknown. In the brains of people with Parkinson’s, the protein alpha-synuclein forms clumps known as Lewy bodies. Scientists have observed that Lewy bodies sometimes seem to spread among neighboring neurons, but it was not understood exactly how this occurred. Some studies indicated that damaged proteins might travel from cell to cell — the “contagious protein” hypothesis of Parkinson’s. But these experiments used neurons in cell culture with artificially high levels of alpha-synuclein.
Researchers led by Virginia M.-Y. Lee, Ph.D., at the University of Pennsylvania School of Medicine wanted to find out if toxic clumps of alpha-synuclein could enter human brain cells making normal amounts of alpha-synuclein and still mock the features of Parkinson’s. So Dr. Lee and her colleagues added alpha-synuclein fibrils — the precursors of Lewy bodies — to mouse neurons growing in a Petri dish, and observed whether the healthy neurons developed a Parkinson’s-like pathology.
- Alpha-synuclein fibrils were taken up by the healthy neurons. Once inside, the fibrils caused alpha-synuclein produced by the cells to clump together into Parkinson’s-like Lewy bodies.
- Alpha-synuclein clumps initially formed within the axon (the end of the cell) and then spread into the cell body.
- The Lewy bodies interfered with the neuron’s functioning and eventually killed them.
- Older neurons, which produce more alpha-synuclein than younger neurons, were more susceptible to Lewy body formation.
What Does it Mean?
This study may shed light on the mechanisms by which Parkinson’s progresses. With this tool in hand, scientists may be able to test drugs that disrupt Lewy body formation or block their spread from cell to cell, and hence slow down disease progression.
The new model more closely simulates the formation and spread of Lewy bodies in the brain than any other cell culture model to date. However, these experiments were still conducted using mouse neurons in a dish, and it is likely that much remains to be learned about exactly how Lewy bodies form and spread in the human brain.
Reference: Volpicelli-Daley L, Luk K, Patel T, Tanik S, Riddle D, Stieber A, Meaney D, Trojanowski JQ, Lee VM-Y. Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death. Neuron 2011;72(1):57–71.
Source Date: Nov 04 2011