Therapeutically targeting α-synuclein toxicity. Various pathways have been manipulated to decrease α-synuclein toxicity, largely in mouse models of α-synuclein toxicity. These include (i) reducing α-synuclein synthesis with siRNAs, (ii) increasing α-synuclein degradation, (iii) reducing α-synuclein aggregation, (iv) blocking α-synuclein propagation and (v) active immunization of α-synuclein. Drug development to increase lysosomal activity via glucocerebrosidase (GCase) to accelerate α-synuclein degradation, as well as clinical trials using both passive and active immunization against α-synuclein, are currently under way.