Inhibiting β-Amyloid-Associated Alzheimer’s Pathogenesis In Vitro and In Vivo by a Multifunctional Dimeric Bis(12)-hupyridone Derived from Its Natural Analogue

doi:10.1007/s12031-014-0458-5

	Inhibiting β-Amyloid-Associated Alzheimer’s Pathogenesis In Vitro and In Vivo by a Multifunctional Dimeric Bis(12)-hupyridone Derived from Its Natural Analogue
	Hu S.; Wang R.; Cui W.; Zhang Z.; Mak S.; Xu D.; Choi C.; Tsim K.W.; Carlier P.R.; Lee M.; Han Y.
	2015
Source Publication	Journal of Molecular Neuroscience
ISSN	8958696
Volume	55 Issue:4 Pages:1014
Abstract	Fibrillar aggregates of β-amyloid protein (Aβ) is the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer’s disease (AD). Compounds that could inhibit the formation of Aβ fibrils and block Aβ fibrils-associated toxicity may have therapeutic potential to combat AD. Bis(12)-hupyridone (B12H) is a multifunctional homodimer derived from huperzine A, which is an anti-AD drug in China. In the current study, the inhibitory effect of B12H on the formation of Aβ fibrils and their associated toxicity was investigated both in vitro and in vivo. By using Thioflavin T fluorescence assay, we found that B12H (0.3–3 μM) directly inhibited Aβ fibrils formation following co-incubation of B12H and Aβ1–40 at 37 °C for 6 days in vitro. However, huperzine A, at the same concentrations, did not show significant inhibitory effect on Aβ1–40 fibrils formation. Moreover, B12H markedly reduced Aβ1–40-induced cytotoxicity in cultured SH-SY5Y cells, as evidenced by the increase in cell viability, the decrease in lactate dehydrogenase release, and the reduction of apoptotic nuclei. Most importantly, B12H (0.2 and 0.4 mg/kg) reduced intracerebroventricular Aβ1–40 infusion-induced cognitive and memory impairments in rats, as evidenced by the decrease in escape latency and the increase in the spatial bias in Morris water maze test along with increasing choline acetyltransferase activity and decreasing acetylcholinesterase activity. Collectively, our study provided novel sights into the potential application of B12H in AD treatment. © 2014, Springer Science+Business Media New York.
Keyword	Alzheimer’s disease Aβ fibrils Bis(12)-hupyridone Cell viability Memory impairment Thioflavin T
DOI	10.1007/s12031-014-0458-5
URL	View the original
Language	英语
The Source to Article	Scopus
全文获取链接	View Full-Text via DOI View Full-Text via Web of Science View Full-Text via Scopus
引用统计	被引频次[WOS]：13 [WOS记录] [WOS相关记录]
Document Type	Journal article
专题	University of Macau
推荐引用方式 GB/T 7714	Hu S.,Wang R.,Cui W.,et al. Inhibiting β-Amyloid-Associated Alzheimer’s Pathogenesis In Vitro and In Vivo by a Multifunctional Dimeric Bis(12)-hupyridone Derived from Its Natural Analogue[J]. Journal of Molecular Neuroscience,2015,55(4):1014.
APA	Hu S..,Wang R..,Cui W..,Zhang Z..,Mak S..,...&Han Y..(2015).Inhibiting β-Amyloid-Associated Alzheimer’s Pathogenesis In Vitro and In Vivo by a Multifunctional Dimeric Bis(12)-hupyridone Derived from Its Natural Analogue.Journal of Molecular Neuroscience,55(4),1014.
MLA	Hu S.,et al."Inhibiting β-Amyloid-Associated Alzheimer’s Pathogenesis In Vitro and In Vivo by a Multifunctional Dimeric Bis(12)-hupyridone Derived from Its Natural Analogue".Journal of Molecular Neuroscience 55.4(2015):1014.