Animal models of Parkinson's disease and L-dopa induced dyskinesia: how close are we to the clinic?

摘要

BACKGROUND: Several different animal models are currently used to research the neurodegenerative movement disorder Parkinson's disease (PD). RESULTS: Models based on the genetic deficits associated with a small percentage of sufferers demonstrate the pathological accumulation of alpha-synuclein characteristic of the disease but have few motor deficits and little neurodegeneration. Conversely, toxin-based models recreate the selective nigrostriatal cell death and show extensive motor dysfunction. However, these toxin models do not reproduce the extra-nigral degeneration that also occurs as part of the disease and lack the pathological hallmark of Lewy body inclusions. DISCUSSION: Recently, several therapies that appeared promising in the MPTP-treated non-human primate and 6-OHDA-lesioned rat models have entered clinical trials, with disappointing results. We review the animal models in question and highlight the features that are discordant with PD, discussing if our search for pharmacological treatments beyond the dopamine system has surpassed the capacity of these models to adequately represent the disease.