Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amphetamine / pharmacology
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Amyloid beta-Protein Precursor / drug effects
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Amyloid beta-Protein Precursor / metabolism
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Animals
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Antibodies / pharmacology
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Caspase 3
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Caspases / drug effects
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Caspases / metabolism
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Cell Survival / drug effects
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Cell Survival / physiology
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DNA Fragmentation / drug effects
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DNA Fragmentation / physiology
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Disease Models, Animal
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Dopamine / metabolism*
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Fluorescent Dyes / pharmacology
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Genetic Vectors / physiology
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Immunohistochemistry
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Male
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Movement Disorders / drug therapy
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Movement Disorders / etiology
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Movement Disorders / physiopathology
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Neostriatum / metabolism*
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Neostriatum / pathology
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Neostriatum / physiopathology
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Nerve Degeneration / drug therapy*
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Nerve Degeneration / metabolism
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Nerve Degeneration / physiopathology
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Nerve Tissue Proteins / genetics*
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Neural Pathways / metabolism*
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Neural Pathways / pathology
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Neural Pathways / physiopathology
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Neuronal Apoptosis-Inhibitory Protein
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Neurotoxins / pharmacology
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Oxidopamine / pharmacology
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / metabolism
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Parkinsonian Disorders / physiopathology
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Rats
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Rats, Wistar
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Substantia Nigra / metabolism*
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Substantia Nigra / pathology
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Substantia Nigra / physiopathology
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Sympatholytics / pharmacology
Substances
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Amyloid beta-Protein Precursor
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Antibodies
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Fluorescent Dyes
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Naip6 protein, rat
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Nerve Tissue Proteins
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Neuronal Apoptosis-Inhibitory Protein
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Neurotoxins
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Sympatholytics
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Oxidopamine
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Amphetamine
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Casp3 protein, rat
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Caspase 3
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Caspases
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Dopamine