The interplay between lipids and dopamine on α-synuclein oligomerization and membrane binding.
The deposition of α-syn (α-synuclein) as amyloid fibrils and the selective loss of DA (dopamine) containing neurons in the substantia nigra are two key features of PD (Parkinson's disease). α-syn is a natively unfolded protein and adopts an α-helical conformation upon binding to lipid membrane. Oligomeric species of α-syn have been proposed to be the pathogenic species associated with PD because they can bind lipid membranes and disrupt membrane integrity. DA is readily oxidized to generate reactive intermediates and ROS (reactive oxygen species) and in the presence of DA, α-syn form of SDS-resistant soluble oligomers. It is postulated that the formation of the α-syn:DA oligomers involves the cross-linking of DA-melanin with α-syn, via covalent linkage, hydrogen and hydrophobic interactions. We investigate the effect of lipids on DA-induced α-syn oligomerization and studied the ability of α-syn:DA oligomers to interact with lipids vesicles. Our results show that the interaction of α-syn with lipids inhibits the formation of DA-induced α-syn oligomers. Moreover, the α-syn:DA oligomer cannot interact with lipid vesicles or cause membrane permeability. Thus, the formation of α-syn:DA oligomers may alter the actions of α-syn which require membrane association, leading to disruption of its normal cellular function.
Chi L L
CL
Pham
Roberto
R
Cappai
D002462:Cell Membrane; D002463:Cell Membrane Permeability; D004298:Dopamine / Q000737:chemistry*; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D055503:Protein Multimerization; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry*
D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D010743:Phospholipids; D013501:Surface-Active Agents; D051844:alpha-Synuclein; D012967:Sodium Dodecyl Sulfate; C007740:fluorexon; D004298:Dopamine