Figure 1

Models of α-syn aggregation and LBs formation. A α-Syn is present in the vesicle lumen and in the cytoplasma as an intrinsically disordered protein. α-Syn bound to membranes has distinct conformation such as an extended α-helix or a broken-helix. In the pathological context, disordered monomers may lead to oligomerization and fibril formation, following a nucleation-dependent process, in which monomers are added to existing aggregates. B Rotenone administration in rats, A53T α-syn transgenesis in mice and Smad3 deficient mice are interesting models to study LB formation. While A53T α-syn transgenesis and Smad3 deficiency can modulate DA metabolism, rotenone and Smad3 deficiency induce oxidative stress, mechanisms that may participate in LBs formation. Indeed, proteasome and autophagy inhibitors may impair degradation of α-syn. LRRK2 mutations may participate in LB formation by altering autophagy and α-syn solubility.