Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (α)-synuclein. In different conditions, α-synuclein can assume conformations rich in either α-helix or β-sheets. The mechanisms of α-synuclein misfolding, aggregation, and fibrillation remain unknown, but it is thought that β-sheet conformation of α-synuclein is responsible for its associated toxic mechanisms. To gain fundamental insights into the process of α-synuclein misfolding and aggregation, the secondary structure of this protein in the presence of charged and non-charged surfactant solutions was characterized. The selected surfactants were (anionic) sodium dodecyl sulphate (SDS), (cationic) cetyltrimethylammonium chloride (CTAC), and (uncharged) octyl β-D-glucopyranoside (OG). The effect of surfactants in α-synuclein misfolding was assessed by ultra-structural analyses, in vitro aggregation assays, and secondary structure analyses. The α-synuclein aggregation in the presence of negatively charged SDS suggests that SDS-monomer complexes stimulate the aggregation process. A reduction in the electrostatic repulsion between N- and C-terminal and in the hydrophobic interactions between the NAC (non-amyloid beta component) region and the C-terminal seems to be important to undergo aggregation. Fourier transform infrared spectroscopy (FTIR) measurements show that β-sheet structures comprise the assembly of the fibrils.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, afterAlzheimer’s disease
This protein participates in the trafficking of synaptic vesicles and in the regulation of vesicle exocytosis. α-synuclein can act like a chaperone and controls protein degradation and the assembly and distribution of the SNARE–protein complexes, which is directly associated with the release of neurotransmitters, including dopamine [6,7]
At concentrations above the Critical micelle concentration (CMC), sodium dodecylsulfate (SDS) inhibits the aggregation of α-synuclein
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, after. Α-synuclein is a presynaptic neuronal protein that may contribute to PD pathogenesis [3,4]. The normal function of α-synuclein is poorly understood. It has been described that α-synuclein is involved in many synaptic processes [5]. This protein participates in the trafficking of synaptic vesicles and in the regulation of vesicle exocytosis. Α-synuclein can act like a chaperone and controls protein degradation and the assembly and distribution of the SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors)–protein complexes, which is directly associated with the release of neurotransmitters, including dopamine [6,7]. Other attributed functions of α-synuclein include fatty acid binding, physiological regulation of several enzymes, and neuronal survival [8]
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