[ Back to EurekAlert! ] Public release date: 16-Nov-2012
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Contact: Natasha Pinol
American Association for the Advancement of Science

Misfolded proteins cause Parkinson’s-like condition in healthy mice

This is the micrograph showing a pigmented neuron from the substantia nigra of a patient with Parkinson's disease.

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New research may help clear up a controversial issue in Parkinson’s research, about the role that abnormal “alpha-synuclein” proteins play in the disease. Scientists now report that injecting these misfolded proteins into the brains of healthy mice brought about key symptoms of Parkinson’s disease. The buildup of these abnormal protein clumps inside neurons is a hallmark of Parkinson’s and other related diseases. These clumps are called Lewy bodies and Lewy neurites, and they are associated with the massive loss of certain neurons in the substantia nigra pars compacta (SNpc) and other brain regions. But, a cause-and-effect relationship between Lewy body/neurite formation and neurodegeneration remains unclear. Adding to the complexity, neither transgenic nor neurotoxin-based animal models of Parkinson’s disease fully produce the effects that the disease does in humans. Kelvin Luk and colleagues injected synthetic alpha-synuclein fibrils generated from recombinant mouse alpha-synuclein protein into the brains of normal mice. They found misfolded alpha-synuclein caused the formation of Parkinson’s disease-like Lewy bodies and neurites, and subsequent cell-to-cell transmission of abnormal alpha-synuclein to other, connected brain regions including the SNpc. These effects led to the progressive loss of dopaminergic neurons and culminated in movement deficits similar to those in Parkinson’s disease. It thus appears that abnormal alpha-synuclein protein does play a causative role in the development of Parkinson’s disease.


Article #16: "Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice," by K.C. Luk; V. Kehm; J. Carroll; B. Zhang; P. O’Brien; J.Q. Trojanowski; V.M.-Y. Lee at University of Pennsylvania Perelman School of Medicine in Philadelphia, PA.

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