TY - JOUR
T1 - NAIP protects the nigrostriatal dopamine pathway in an intrastriatal 6-OHDA rat model of Parkinson's disease
AU - Crocker, Stephen J.
AU - Wigle, Nichola
AU - Liston, Peter
AU - Thompson, Charlie S.
AU - Lee, Chris J.
AU - Xu, Daigen
AU - Roy, Sophie
AU - Nicholson, Donald W.
AU - Park, David S.
AU - MacKenzie, Alex
AU - Korneluk, Robert G.
AU - Robertson, George S.
PY - 2001
Y1 - 2001
N2 - Parkinson's disease (PD) is a progressive neurodegenerative disorder of the basal ganglia, associated with the inappropriate death of dopaminergic neurons of the substantia nigra pars compacta (SNc). Here, we show that adenovirally mediated expression of neuronal apoptosis inhibitor protein (NAIP) ameliorates the loss of nigrostriatal function following intrastriatal 6-OHDA administration by attenuating the death of dopamine neurons and dopaminergic fibres in the striatum. In addition, we also addressed the role of the cysteine protease caspase-3 activity in this adult 6-OHDA model, because a role for caspases has been implicated in the loss of dopamine neurons in PD, and because NAIP is also a reputed inhibitor of caspase-3. Although caspase-3-like proteolysis was induced in the SNc dopamine neurons of juvenile rats lesioned with 6-OHDA and in adult rats following axotomy of the medial forebrain bundle, caspase-3 is not induced in the dopamine neurons of adult 6-OHDA-lesioned animals. Taken together, these results suggest that therapeutic strategies based on NAIP may have potential value for the treatment of PD.
AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder of the basal ganglia, associated with the inappropriate death of dopaminergic neurons of the substantia nigra pars compacta (SNc). Here, we show that adenovirally mediated expression of neuronal apoptosis inhibitor protein (NAIP) ameliorates the loss of nigrostriatal function following intrastriatal 6-OHDA administration by attenuating the death of dopamine neurons and dopaminergic fibres in the striatum. In addition, we also addressed the role of the cysteine protease caspase-3 activity in this adult 6-OHDA model, because a role for caspases has been implicated in the loss of dopamine neurons in PD, and because NAIP is also a reputed inhibitor of caspase-3. Although caspase-3-like proteolysis was induced in the SNc dopamine neurons of juvenile rats lesioned with 6-OHDA and in adult rats following axotomy of the medial forebrain bundle, caspase-3 is not induced in the dopamine neurons of adult 6-OHDA-lesioned animals. Taken together, these results suggest that therapeutic strategies based on NAIP may have potential value for the treatment of PD.
UR - http://www.scopus.com/inward/record.url?scp=0034883987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034883987&partnerID=8YFLogxK
U2 - 10.1046/j.0953-816X.2001.01653.x
DO - 10.1046/j.0953-816X.2001.01653.x
M3 - Article
C2 - 11553289
AN - SCOPUS:0034883987
SN - 0953-816X
VL - 14
SP - 391
EP - 400
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 2
ER -