Modulation of α-synuclein expression in transgenic animals for modelling synucleinopathies — is the juice worth the squeeze?

Studies of various animal models have made a substantial contribution to the recent progress in understanding the molecular and cellular basis of neurodegenerative disorders. Modelling of neuro-degeneration by genetic alteration of laboratory animals became one of the most powerful tools of modern experimental neurology. The crucial event in pathogenesis of neurodegenerative diseases known as synucleinopathies is modification of α-synuclein metabolism caused by missense mutations, increased expression of the gene, or impaired degradation or intracellular compart-mentalisation of the protein. Therefore, manipulations with expression of α-synuclein in laboratory animals were widely used for creating models of these diseases. In the present review we discuss strong and weak sides of such models, what has been already learned from studies of these animals and what types of models might be useful to further our knowledge about pathogenesis of different synucleinopathies.