Dopamine-Induced α-Synuclein Oligomers

Abstract α-Synuclein (α-syn) is a 140-residue natively unfolded protein; its physiologic role is not yet elucidated, although it has been implicated in a number of neurodegenerative disorders, including Parkinson’s disease (PD), dementia with Lewy bodies (LB) and the LB variant of Parkinson’s disease. PD is characterized by a selective loss of dopaminergic neurons and the presence of insoluble α-syn aggregates, i.e. amyloid fibrils, deposited in LBs in the remaining substantia nigra pars compacta neurons of the mid-brain. This region contains neurons whose main neurotransmitter is dopamine (DA) and thus plays a role in reward-driven learning and control of movement and balance. This chapter focuses on the interaction of α-syn and DA, in particular on the resulting soluble oligomers, their structure, properties and potential role in the development and prevention of PD.