Evidence map›Paper›PMID 26401780›Full record

ArticleJournal of Alzheimer's disease : JAD2015

Bivalent Compound 17MN Exerts Neuroprotection through Interaction at Multiple Sites in a Cellular Model of Alzheimer's Disease.

Kai Liu, Jeremy E Chojnacki, Emily E Wade, John M Saathoff, Edward J Lesnefsky, Qun Chen, Shijun Zhang

Abstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Kai LiuDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
Jeremy E ChojnackiDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
Emily E WadeDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
John M SaathoffDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
Edward J LesnefskyDepartment of Medicine, Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University, Richmond, VA, USA.
Qun ChenDepartment of Medicine, Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University, Richmond, VA, USA.
Shijun ZhangDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
Virginia Commonwealth University · US

Funding

VCU Neuroscience Center Core GrantP30NS047463 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI POVLISHOCK, JOHN T · 2003 to 2013
$5.0M
Novel bivalent multifunctional ligands towards Alzheimer's diseaseR01AG041161 · NIA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, SHIJUN · 2012 to 2016
$1.5M
Reduction of cardiac injury by targeting damaged mitochondria during reperfusionI01BX001355 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI LESNEFSKY, EDWARD J · 2012 to 2025
–
BLRD VA I01 BX001355NCI NIH HHS P30 CA01605NIA NIH HHS R01 AG041161NIA NIH HHS R01AG041161NINDS NIH HHS 5 P30 NS047463NINDS NIH HHS P30 NS047463
6 · The paper itself

Abstract

Multiple pathogenic factors have been suggested to play a role in the development of Alzheimer's disease (AD). The multifactorial nature of AD also suggests the potential use of compounds with polypharmacology as effective disease-modifying agents. Recently, we have developed a bivalent strategy to include cell membrane anchorage into the molecular design. Our results demonstrated that the bivalent compounds exhibited multifunctional properties and potent neuroprotection in a cellular AD model. Herein, we report the mechanistic exploration of one of the representative bivalent compounds, 17MN, in MC65 cells. Our results established that MC65 cells die through a necroptotic mechanism upon the removal of tetracycline (TC). Furthermore, we have shown that mitochondrial membrane potential and cytosolic Ca2+ levels are increased upon removal of TC. Our bivalent compound 17MN can reverse such changes and protect MC65 cells from TC removal induced cytotoxicity. The results also suggest that 17MN may function between the Aβ species and RIPK1 in producing its neuroprotection. Colocalization studies employing a fluorescent analog of 17MN and confocal microscopy demonstrated the interactions of 17MN with both mitochondria and endoplasmic reticulum, thus suggesting that 17MN exerts its neuroprotection via a multiple-site mechanism in MC65 cells. Collectively, these results strongly support our original design rationale of bivalent compounds and encourage further optimization of this bivalent strategy to develop more potent analogs as novel disease-modifying agents for AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsApoptosisBrainCalciumCaspase 3Cell Line, TumorCholesterolCurcuminEndoplasmic ReticulumHumansMaleMembrane Potential, MitochondrialMice, Inbred C57BLMolecular Structure17MN compoundAmyloid beta-Peptidesamyloid beta-protein (1-40)CalciumCASP3 protein, humanCaspase 3CholesterolCurcuminNeuroprotective AgentsPeptide FragmentsReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanAlzheimer’s diseasebivalent compoundcalciummitochondriamultifunctionalneuroprotection

Identifiers

PMID26401780
PMCPMC4829378
OpenAlexW2258747760

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.