Agonizing over dopaminergic replacement therapy--lessons from animal models of Parkinson's disease.

Pacific Parkinson's Research Centre, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5.
Experimental Neurology (Impact Factor: 4.62). 10/2003; 183(1):1-3. DOI: 10.1016/S0014-4886(03)00184-5
Source: PubMed
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    ABSTRACT: Background: Pramipexole is one of a new generation of dopamine agonists. Recently there have been questions regarding its neuroprotective effects. These effects have been tested against various insults, which have yielded conflicting results.Methods: In this study, we introduced a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/paraquat to induce a severe Parkinson's disease model. The mice, after receiving the combination of toxins, were evaluated using mortality rates and immunohistochemistry for degenerating tyrosine hydroxylase-positive neurons.Results and conclusions: Pramipexole was tested for its capacity to offer protection against neurotoxic the effects of MPTP/paraquat in this model; however, the results showed no improvement with pramipexole therapy.
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    ABSTRACT: With increased understanding of disease pathogenesis and the foreseeable reality of disease-modifying therapies, there is a growing need to find biomarkers that will allow early (preferably preclinical) detection of disease and that will provide an independent readout of disease progression. In this article, we review a variety of markers, with a focus on functional imaging techniques, which while imperfect, currently provide the best approach to this problem. We consider the limitations of functional imaging of the dopamine system in assessing the progression of Parkinson's Disease (PD) as well as the potential use of structural imaging and emerging progress in other biochemical and molecular markers. While there is no single biomarker that will satisfy all requirements, some combination is likely to be of great use in identifying those subjects most likely to benefit from neuroprotective therapies, as well as in monitoring the effects of these interventions. © 2012 Movement Disorder Society.
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