Structure of α-synuclein and a model of α-synuclein aggregation and toxicity. The modular structure of α-synuclein, illustrating the location of familial-associated mutations and other key features of α-synuclein, including the imperfect (KTKEGV) repeats (R), is depicted in the top panel. The bottom panel shows a model of α-synuclein aggregation and toxicity and the proposed factors that enhance (+) or inhibit (–) the formation of toxic aggregated forms of α-synuclein. DA enhances the formation of the protofibrillar form of α-synuclein and prevents it from aggregating into the fibrillar form (not shown).