The present invention provides novel methods for the treatment of Parkinson's disease and other .alpha.-synucleinopathies. The methods of the invention include treatment with inhibitors of transglutaminase, which can inhibit aggregation of .alpha.-synuclein. Also provided are screening assays for novel inhibitors of transglutaminase which may be used in the treatment of Parkinson's disease and other .alpha.-synucleinopathies.