The abnormal accumulation of α-synuclein aggregates in neurons, nerve fibers, or 
glial cells is the hallmark of a group of neurodegenerative diseases known 
collectively as α-synucleinopathies. Clinical, neuropathological, and 
experimental evidence strongly suggests that α-synuclein plays a role not only 
as a trigger of pathological processes at disease inception, but also as a 
mediator of pathological spreading during disease progression. Specific 
properties of α-synuclein, such as its ability to pass from one neuron to 
another, its tendency to aggregate, and its potential to generate 
self-propagating species, have been described and elucidated in animal models 
and may contribute to the relentless exacerbation of Parkinson's disease 
pathology in patients. Animal models used for studying α-synuclein accumulation, 
aggregation, and propagation are mostly based on three approaches: (1) 
intra-parenchymal inoculations of exogenous α-synuclein (e.g., synthetic 
α-synuclein fibrils), (2) transgenic mice, and (3) animals (mice or rats) in 
which α-synuclein overexpression is induced by viral vector injections. Whereas 
pathological α-synuclein changes are consistently observed in these models, 
important differences are also found. In particular, pronounced pathology in 
transgenic mice and viral vector-injected animals does not appear to involve 
self-propagating α-synuclein species. A critical discussion of these models 
reveals their strengths and limitations and provides the basis for 
recommendations concerning their use for future investigations.