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Fractalkine Over Expression Suppresses α-Synuclein-mediated Neurodegeneration.

Mol Ther Methods Clin Dev.. 2014-12;  23(1):17?C23
K R Nash, P Moran, D J Finneran, C Hudson, J Robinson, D Morgan and P C Bickford. Molecular Pharmacology and Physiology Department, Byrd Alzheimer Institute, University of South Florida, 4001 E Fletcher Ave, Tampa, Florida 33613, USA.
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摘要

In Parkinson's disease, α-synuclein is known to activate microglia and this activation has been proposed as one of the mechanisms of neurodegeneration. There are several signals produced by neurons that have an anti-inflammatory action on microglia, including CX3CL1 (fractalkine). We have shown that a soluble form of CX3CL1 is required to reduce neuron loss in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and that fractalkine agonism can reduce neuron loss in a 6-hydroxydopamine lesion model. Here, we show that fractalkine can reduce α-synuclein-mediated neurodegeneration in rats. Rats that received fractalkine showed abrogated loss of tyrosine hydroxylase and Neu-N staining. This... More

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