Kinesin-1 inhibits the aggregation of amyloid-beta peptide as detected by fluorescence cross-correlation spectroscopy

摘要

Although the exact etiology and pathogenesis of Alzheimer's disease (AD) are still unclear, amyloid-beta (A beta) generated by the proteolytic processing of amyloid-b precursor protein (APP) aggregate to form toxic amyloid species. Kinesin-1 is the first identified ATP-dependent axonal transport motor protein that has been proven to affect A beta generation and deposition. In this paper, we applied dual-color fluorescence cross-correlation spectroscopy (DC-FCCS) to investigate the direct interaction of A beta with kinesin-1 at the single-molecule fluorescence level in vitro. The results showed that two kinds of enhanced green fluorescent protein (EGFP)-tagged kinesin light-chain subunits of kinesin-1(KLCs), KLC-E and E-KLC inhibited the aggregation of A beta over a period of time, providing additional insight into the mechanism of axonal transport deficits in AD.