Inhibition of Aß fibril formation on a reconstituted lipid bilayer by a GM1 cluster-binding peptide
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1
Keio University, Faculty of Science and Technology, Japan
The deposition of the amyloid ß protein (Aß) is a critical step in the pathogenesis of Alzheimer’s disease (AD). Aß has been reported to bind to the monosialoganglioside GM1 cluster in neuronal membranes and forms toxic oligomers and fibrils. The mechanism underlying Aß deposition has been investigated and the characterization of Aß oligomers has been performed; however, few fundamental therapeutic agents currently exist for AD. We focused on the GM1 cluster to which Aß binds because of its potential as a major therapeutic target against AD. In the present study, we used a GM1 cluster-binding peptide identified by a phage display method as an inhibitor. We constructed a GM1-containing lipid bilayer (GM1/sphingomyelin/cholesterol =10:45:45), and the interaction between Aß and the peptide on the membrane was investigated by atomic force microscopy (AFM). We found that the number of Aß fibrils decreased in the presence of the GM1 cluster-binding peptide. We also showed that Aß fibril formation was inhibited by the GM1 cluster-binding peptide before and after the administration of Aß. Furthermore, a four-branched peptide dendrimer showed a high affinity for GM1 and inhibited Aß fibril formation. These results suggest the potential of the GM1 cluster-binding peptide as a novel prophylactic and therapeutic agent for AD.
Keywords:
neurodegeneration,
Lipid,
Therapeutic agent,
Prophylactic agent,
amyloid ß protein
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
Poster Presentation Session
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
Nakai
M,
Nishihara
M,
Matsubara
T and
Sato
T
(2016). Inhibition of Aß fibril formation on a reconstituted lipid bilayer by a GM1 cluster-binding peptide.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00130
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Received:
04 Aug 2016;
Published Online:
11 Aug 2016.
*
Correspondence:
Ms. Mako Nakai, Keio University, Faculty of Science and Technology, Yokohama, Kanagawa, Japan, get.glory.days@gmail.com