Breaking down and building up alpha-synuclein: An insight on its N-terminal domain

Alpha-synuclein (alpha Syn) is a small presynaptic protein (14 kDa) that is involved in synucleinopathies including Parkinson's disease (PD). In its native state, the alpha Syn monomer exists in an unfolded state, and its folding is highly dependent on variations of environmental conditions, mutations and interactions with endogenous and/or exogenous molecules. Recently, there is increasing evidence for a direct interplay between alpha Syn and microtubules (MTs), whose defects are linked to neurodegenerative diseases, such as PD. Understanding the correlation between alpha Syn and MTs could be fundamental for the correct comprehension of the undergoing mechanisms of PD. Hence, we chemically synthesized a library of peptides, deriving from both native and PD mutated sequences of the N-terminal domain of alpha Syn. Their secondary structure was characterized by circular dichroism and Fourier transform infrared (FTIR) experiments, in order to evaluate the effect of PD mutations. Finally, the kinetics of polymerizing tubulin in vitro in the presence of the peptides was evaluated. A library of peptides, deriving from both native and Parkinson's disease (PD) mutated sequences of the N-terminal domain of alpha-synuclein (alpha Syn), was synthesized. Their secondary structure was characterized in order to evaluate the effect of PD mutations. The kinetics of polymerizing tubulin in vitro in the presence of the peptides was evaluated.image