Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice
- Crocker, S.J. (S. J.)
- Liston, P. (P.)
- Anisman, H. (Hymie)
- Lee, C.J. (C. J.)
- Smith, P. (Patrice D.)
- Earl, N. (N.)
- Thompson, C.S. (C. S.)
- Park, D.S. (D. S.)
- Korneluk, R.G. (R. G.)
- Robertson, G.S. (G. S.)
DOIAbstract
X-linked IAP protein is a potent inhibitor of cell death. Here, we describe a novel transgenic mouse in which the human XIAP gene is expressed under the control of the neuron-specific enolase promoter (NSE-xiap). We demonstrate that nigrostriatal dopamine neurons of NSE-xiap mice were resistant to the damaging effects of the dopaminergic neurotoxin MPTP. MPTP-induced reduction of striatal dopamine metabolism was also attenuated in NSE-xiap mice. Furthermore, NSE-xiap mice treated with MPTP did not exhibit deficits in exploratory behaviour in an open-field test. Taken together, these findings suggest that strategies to enhance neuronal expression of XIAP may provide therapeutic benefit for the treatment of neurodegeneration in Parkinson's di...
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