Surface Chemistry and Spectroscopic Study of the Nonamyloid-Beta Component Segment of α-Synuclein (61-95)

Abstract

Parkinson’s disease is a neurodegenerative disorder, characterized by a progressive loss of the dopaminergic neurons in the substantia nigra portion of the mid brain. The degenerating dopaminergic neurons develop a hallmark deposition of Lewy bodies comprising of mostly abundant of α-synuclein, which is a protein of 140 amino acid residues. The primary structure of α-synuclein is divided into three parts: N-terminal residues 1-60; the nonamyloid-beta component (NAC) which spans residues 61-95 and is responsible for the aggregation; and residues 96-140 which comprise the negatively charged C-terminus.34 Though, there is an abundance of α-synuclein (~ 1 % among the total proteins) in the brain, α-synuclein accumulates in the presynaptic terminals where high concentration of amphiphilic structure such as liposomes and cell membrane. Previously, α-synuclein has been spread at the air-water interface which was used to mimic the amphiphilic nature in vivo. Both circular dichroism (CD) and FTIR showed that α-synuclein transforms from unstructured conformation in aqueous solution to α-helix at the interface.23 Here, the NAC part of α-synuclein (i.e., α-synuclein (61-95)) was synthesized and purified. α-Synuclein (61-95) was shown to form a stable Langmuir monolayer at the air-water interface. The CD results, show that α-synuclein (61-95) transforms from unstructured conformation in aqueous solution to α-helix at the air-water interface. Also, surface FTIR techniques have shown a parallel orientation of the helical axis of α-synuclein (61-95) to the interface.