Parkinson’s disease is the second most common neurodegenerative disease and is characterized by a progressive loss of the dopaminergic neurons in <i>substantia nigra</i>. The degenerating dopaminergic neurons develop a hallmark deposition of Lewy bodies comprising abundant abnormal aggregates (i.e., fibrils) of α-synuclein (α-syn), which is a protein contains 140 amino acid residues. Despite the abundance (~ 1 % among the total proteins) in the brain, α-syn accumulates in the presynaptic terminals where exists high concentration of amphiphilic structure (e.g., lipsomes and cell membrane) and the reason of the accumulation is not clear. On the other hand, the primary structure of α-syn constitutes three domains: N-terminal residues 1–60; the nonamyloid component (NAC) which spans residues 61–95 and is responsible for the aggregation; and residues 96–140 which comprise the negatively charged C-terminus. Here, both α-syn and its NAC part (i.e., α-syn(61-95)) were synthesized and purified. α-Syn and α-syn(61-95) were shown to be able to form a stable Langmuir monolayer at the air-water interface by Langmuir technique, which utilizes air-water interface to mimic the amphiphilic structure in vivo. From circular dichoism and FTIR results, both α-syn and α-syn(61-95) transform from unstructured conformation in aqueous solution to α-helix at the interface. Because α-helix is stable at the interface, this transformation explains the reason of the accumulation of α-syn around the amphiphilic structure. α-Syn(61-95), the NAC part of α-syn, did not aggregate at the interface. This also suggests the amphiphilic structure stabilizes α-syn and inhibits its aggregation. The onset of Parkinson’s disease may be due to the lost of amphiphilic structure (such as phospholipids) in the brains of aging people.

Surface chemistry and spectroscopy study of α-synuclein and the NAC part

256th National Meeting (2018)

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