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The protein a-synuclein accumulates in the brain of people with Parkinson's disease. In addition, the cells that produce the neurotransmitter dopamine deteriorate in these patients. However, it's not clear why dopaminergic neurons are selectively destroyed in Parkinson's disease. Uncertainty also surrounds the role of a-synuclein in the neurodegeneration. Dopamine metabolism generates reactive oxygen species that damage cellular proteins, leading to apoptosis (death) of neurons. Cells can resist the initiation of apoptosis with the help of a family of protein chaperones called 14-3-3. However, 14-3-3 can't effect a cellular rescue if it's tied up elsewhere. The researchers suggest that, in Parkinson's patients, a-synuclein binds to 14-3-3, reducing its availability for antiapoptotic activity. "This may, in turn, increase neuronal vulnerability to reactive oxygen species generated by endogenous dopamine metabolism," they say.
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