Characterization of the interaction of a truncated form of alpha-synuclein with membrane by biophysical methods

Parkinson's disease (PD) is a chronic disorder associated with the degeneration of dopaminergic neurons in the substantia nigra pars-compacta. A key feature of PD is the presence of Lewis Bodies (LBs) inclusions, which are primarily composed of aggregates of -Synuclein (Syn). Syn is an intrinsically disordered protein, highly abundant in pre-synaptic neurons where it has a role in synaptic vesicle traffic and turnover; it adopts a range of conformations, alternating between the free random coil state and the membrane-bound -helical form. The N-terminal region of Syn has been observed to be crucial for the protein’s physiological function, particularly in regulating vesicle cycling and neurotransmitter release at presynaptic termini. Consistent with this function, alteration to the sequence of the N-terminal region can impact the membrane-binding ability. In this project, the attention is focused on the study of a truncated version (7-140) of Syn, optimizing its production in vitro. Furthermore, the role of residues 1 to 6 in the N-terminal region of Syn is investigated in terms of its ability to regulate the interaction with membranes, comparing the interaction of Syn with biological membranes and its truncated form, the fragment 7-140. In this work all the analysis were performed by exploiting innovative biophysical and biochemical technologies.