Construction of Self-Assembling Lipopeptide-Based Benign Nanovesicles to Prevent Amyloid Fibril Formation and Reduce Cytotoxicity of GxxxGxxxGxxxG Motif.

ABSTRACT

Alzheimer's disease, a progressive severe neurodegenerative disorder, has been until now incurable, in spite of serious efforts worldwide. We have designed self-assembled myristoyl-KPGPK lipopeptide-based biocompatible nanovesicles, which can inhibit amyloid fibrillation made by the transmembrane GxxxGxxxGxxxG motif of Aß-protein and human myelin protein zero as well as reduce their neurotoxicity. Various spectroscopic and microscopic investigations illuminate that the lipopeptide-based nanovesicles dramatically inhibit random coil-to-ß-sheet transformation of Aß25-37 and human myelin protein zero protein precursor, which is the prerequisite of GxxxGxxxGxxxG motif-mediated fibril formation. Förster resonance energy transfer (FRET) assay using synthesized Cy-3 (FRET donor) and Cy-5 (FRET acceptor)-conjugated Aß25-37 also exhibits that nanovesicles strongly inhibit the fibril formation of Aß25-37. The mouse neuro-2a neuroblastoma cell line is used, which revealed the GxxxGxxxGxxxG-mediated cytotoxicity. However, the neurotoxicity has been diminished by co-incubating the GxxxGxxxGxxxG motif with the nanovesicles.