NAIP protects the nigrostriatal dopamine pathway in an intrastriatal 6-OHDA rat model of Parkinson's disease.
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.
Crocker
S J
SJ
Neuroscience Research Institute, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada. crocker@uottawa.ca
Wigle
N
N
Liston
P
P
Thompson
C S
CS
Lee
C J
CJ
Xu
D
D
Roy
S
S
Nicholson
D W
DW
Park
D S
DS
MacKenzie
A
A
Korneluk
R G
RG
Robertson
G S
GS
D000661:Amphetamine / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000494:pharmacology; D005822:Genetic Vectors / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009434:Neural Pathways / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051616:Neuronal Apoptosis-Inhibitory Protein; D009498:Neurotoxins / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013565:Sympatholytics / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D005456:Fluorescent Dyes; C496803:Naip6 protein, rat; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D009498:Neurotoxins; D013565:Sympatholytics; D016627:Oxidopamine; D000661:Amphetamine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D004298:Dopamine