Identification of a New Function of Cardiovascular Disease Drug 3-Morpholinosydnonimine Hydrochloride as an Amyloid-β Aggregation Inhibitor

ACS Omega
Baiping RenJie Zheng

Abstract

Cardiovascular disease (CVD) and Alzheimer's disease (AD) have a mutual cause-and-effect relationship, and they share some common risk factors. Although numerous Food and Drug Administration (FDA)-approved drugs have been developed for CVD treatment, no drugs are clinically available for AD treatment. Given the common disease-causing factors and links between the two diseases and the well-demonstrated drugs for CVD, we propose to re-examine the new potential of the existing CVD drugs as amyloid-β (Aβ) inhibitors. 3-Morpholinosydnonimine hydrochloride (SIN-1) is an FDA-approved drug for inhibiting platelet aggregation in CVD. Herein, we examine the inhibition activity of SIN-1 on the aggregation and toxicity of Aβ1-42 using combined experimental and computational approaches. Collective experimental data from ThT, circular dichroism, and atomic force microscopy demonstrate that SIN-1 can effectively inhibit amyloid formation at every stage of Aβ aggregation by prolonging lag phase, slowing down aggregation rate, and reducing final fibril formation. The cell viability assay also shows that SIN-1 enables the protection of SH-SY5Y cells from Aβ-induced cell toxicity. Such an inhibition effect is attributed to interference with the s...Continue Reading

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Citations

Jan 7, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Baiping RenJie Zheng
Oct 14, 2019·Journal of Pharmaceutical and Biomedical Analysis·Angela De SimoneVincenza Andrisano
Mar 30, 2021·ACS Chemical Neuroscience·Yijing TangJie Zheng
Nov 22, 2017·Langmuir : the ACS Journal of Surfaces and Colloids·Fengyu YangJie Zheng
Dec 7, 2019·Journal of Chemical Information and Modeling·Joseph M JakubowskiPhanourios Tamamis

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Methods Mentioned

BETA
atomic
circular dichroism
AFM
Fluorescence
Assay

Software Mentioned

GaussView
VMD
NAMD
CDPro
CDSSTR
CGenFF
CHARMM scripts
house Tcl
CHARMM
in

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