|
Abstract
|
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, afflicting
nearly 1% of the population over the age of 60 years. Aggregation of α-syn leading to
dopaminergic neuronal death has been recognized as one of the main pathogenic factors in the
initiation and progression of PD. Consequently, α-syn has been targeted for the development of
therapeutics for PD.
Human α-syn is a natively unfolded 140-amino-acidresidue protein widely expressed in
neurons, found predominantly in presynaptic terminals [1-3]. Structurally, α-synuclein features
an N-terminal domain (residues 1–60), a central hydrophobic portion denoted as non-amyloid
beta component (NAC, residues 61–95) and a C-terminal negatively charged region (residues
96–140). NAC domain, is required for alpha-synuclein to polymerize into amyloid filaments,
which are the major components of alpha-synuclein pathological inclusions.
Here we present the mechanisms and kinetics of NAC domain of α-synuclein aggregation
using the molecular dynamics simulation method, as well as crucial factors affecting this process.
The results of the simulation studies were presented as structural data like hydrogen bonding,
interacting residues and various distribution functions as well as energetics of the considered
system. The interaction energies, and the contribution of lennard-Jones and electrostatic
interactions in intarction energy have been also analysed.
|