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Molecules 2016, 21(4), 412; doi:10.3390/molecules21040412

Mechanistic Insight of Bivalent Compound 21MO as Potential Neuroprotectant for Alzheimer’s Disease

1
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA
2
Department of Medicine, Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University, Richmond, VA 23298, USA
3
Department of Biochemistry, Virginia Commonwealth University, Richmond, VA 23298, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Michael Decker and Diego Muñoz-Torrero
Received: 29 January 2016 / Revised: 18 March 2016 / Accepted: 23 March 2016 / Published: 25 March 2016
(This article belongs to the Special Issue Molecules against Alzheimer)
View Full-Text   |   Download PDF [2426 KB, uploaded 25 March 2016]   |  

Abstract

We have recently developed a bivalent strategy to provide novel compounds that potentially target multiple risk factors involved in the development of Alzheimer’s disease (AD). Our previous studies employing a bivalent compound with a shorter spacer (17MN) implicated that this compound can localize into mitochondria and endoplasmic reticulum (ER), thus interfering with the change of mitochondria membrane potential (MMP) and Ca2+ levels in MC65 cells upon removal of tetracycline (TC). In this report, we examined the effects by a bivalent compound with a longer spacer (21MO) in MC65 cells. Our results demonstrated that 21MO suppressed the change of MMP, possibly via interaction with the mitochondrial complex I in MC65 cells. Interestingly, 21MO did not show any effects on the Ca2+ level upon TC removal in MC65 cells. Our previous studies suggested that the mobilization of Ca2+ in MC65 cells, upon withdraw of TC, originated from ER, so the results implicated that 21MO may preferentially interact with mitochondria in MC65 cells under the current experimental conditions. Collectively, the results suggest that bivalent compounds with varied spacer length and cell membrane anchor moiety may exhibit neuroprotective activities via different mechanisms of action. View Full-Text
Keywords: Alzheimer’s disease; bivalent compound; calcium; mitochondria; multifunctional; neuroprotection Alzheimer’s disease; bivalent compound; calcium; mitochondria; multifunctional; neuroprotection
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MDPI and ACS Style

Saathoff, J.M.; Liu, K.; Chojnacki, J.E.; He, L.; Chen, Q.; Lesnefsky, E.J.; Zhang, S. Mechanistic Insight of Bivalent Compound 21MO as Potential Neuroprotectant for Alzheimer’s Disease. Molecules 2016, 21, 412.

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