Modeling with the A53T α-synuclein model of Parkinson's disease

The disease-causing A53T mutation of α-synuclein (PARK1) was adopted to generate and study pathophysiologic effects in several animal models shortly after its discovery. It is used to create transgenic parkinsonian animal models in Drosophila and mice, and it is also possible to deliver A53T α-synuclein via viral vectors directly into a desired brain region such as the substantia nigra and thereby induce progressive nigrostriatal degeneration, which has been performed in rodents and nonhuman primates. All of these models provide powerful tools to examine different aspects of α-synuclein-induced pathophysiology in Parkinson's disease and are also very helpful for the preclinical assessment of disease-modifying drugs or therapeutic interventions. The different aspects and basic principles of A53T α-synuclein animal models are reviewed in this chapter.