Brief Communication -Synuclein Overexpression Protects against Paraquat- Induced Neurodegeneration
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چکیده
-Synuclein is likely to play a role in neurodegenerative processes, including the degeneration of nigrostriatal dopaminergic neurons that underlies Parkinson’s disease. However, the toxicological properties of -synuclein remain relatively unknown. Here, the relationship between -synuclein expression and neuronal injury was studied in mice exposed to the herbicide paraquat. Paraquat neurotoxicity was compared in control animals versus mice with transgenic expression of human -synuclein driven by the tyrosine hydroxylase (TH) promoter. In control mice, paraquat caused both the formation of -synuclein-containing intraneuronal deposits and the degeneration of nigrostriatal neurons, as demonstrated by silver staining and a reduction of the counts of TH-positive and Nissl-stained cells. Mice overexpressing -synuclein, either the human wild-type or the Ala53Thr mutant form of the protein, displayed paraquat-induced protein aggregates but were completely protected against neurodegeneration. These resistant animals were also characterized by increased levels of HSP70, a chaperone protein that has been shown to counteract paraquat toxicity in other experimental models and could therefore contribute to neuroprotection in -synuclein transgenic mice. The results indicate a dissociation between toxicant-induced -synuclein deposition and neurodegeneration. They support a role of -synuclein against toxic insults and suggest that its involvement in human neurodegenerative processes may arise not only from a gain of toxic function, as previously proposed, but also from a loss of defensive properties.
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تاریخ انتشار 2003