Interference of α-synuclein uptake by monomeric β-Amyloid1–40 and potential core acting site of the interference

Daniel K Y Chan*, Nady Braidy, Ying Hua Xu, Tim Chataway, Feng Guo, Gilles J. Guillemin, Charlie Teo, Wei Ping Gai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Increasing evidence suggests an important role of alpha-synuclein (α-Syn) in the pathogenesis of Parkinson’s disease (PD). The inter-neuronal spread of α-Syn via exocytosis and endocytosis has been proposed as an explanation for the neuropathological findings of PD in sub-clinical and clinical phases. Therefore, interfering the uptake of α-Syn by neurons may be an important step in slowing or modifying the propagation of the disease. The purposes of our study were to investigate if the uptake of α-Syn fibrils can be specifically interfered with monomeric β-Amyloid1–40 (Aβ40) and to characterise the core acting site of interference. Using a radioisotope-labelled uptake assay, we found an 80 % uptake reduction of α-Syn fibrils in neurons interfered with monomeric Aβ40, but not β-Amyloid1–42 (Aβ42) as compared to controls. This finding was further confirmed by enzyme-linked immunosorbent assay (ELISA) with α-Syn uptake reduced from about 80 % (Aβ42) to about 20 % (Aβ40) relative to controls. To define the region of Aβ40 peptide capable of the interference, we explored shorter peptides with less amino acid residues from both the C-terminus and N-terminus. We found that the interference effect was preserved if amino acid residue was trimmed to position 11 (from N-terminus) and 36 (from C-terminus), but dropped off significantly if residues were trimmed beyond these positions. We therefore deduced that the “core acting site” lies between amino acid residue positions 12–36. These findings suggest α-Syn uptake can be interfered with monomeric Aβ40 and that the core acting site of interference might lie between amino acid residue positions 12–36.

Original languageEnglish
Pages (from-to)479-485
Number of pages7
JournalNeurotoxicity Research
Volume30
Issue number3
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • α-synuclein
  • β-amyloid 1–40
  • α-synuclein uptake
  • β-amyloid 1–42
  • interference

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