A genome-wide association study in human lymphoblastoid cells supports safety of mitochondrial complex I inhibitor

Huanyao Gao; Utkarsh Tripathi; Sergey Trushin; Lela Okromelidze; Nicholas P. Pichurin; Lixuan Wei; Yongxian Zhuang; Liewei Wang; Eugenia Trushina

doi:10.1016/j.mito.2021.02.005

A genome-wide association study in human lymphoblastoid cells supports safety of mitochondrial complex I inhibitor

Huanyao Gao, Utkarsh Tripathi, Sergey Trushin, Lela Okromelidze, Nicholas P. Pichurin, Lixuan Wei, Yongxian Zhuang, Liewei Wang, Eugenia Trushina

Research output: Contribution to journal › Article › peer-review

Abstract

Novel therapeutic strategies for Alzheimer's disease (AD) are of the greatest priority given the consistent failure of recent clinical trials focused on Aβ or pTau. Earlier, we demonstrated that mild mitochondrial complex I inhibitor CP2 blocks neurodegeneration and cognitive decline in multiple mouse models of AD. To evaluate the safety of CP2 in humans, we performed a genome-wide association study (GWAS) using 196 lymphoblastoid cell lines and identified 11 SNP loci and 64 mRNA expression probe sets that potentially associate with CP2 susceptibility. Using primary mouse neurons and pharmacokinetic study, we show that CP2 is generally safe at a therapeutic dose.

Original language	English (US)
Pages (from-to)	83-94
Number of pages	12
Journal	Mitochondrion
Volume	58
DOIs	https://doi.org/10.1016/j.mito.2021.02.005
State	Published - May 2021

Keywords

Alzheimer's Disease
Genome-wide association study
Lymphoblastoid cell lines
Mitochondrial complex I inhibitor

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Cell Biology

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10.1016/j.mito.2021.02.005

Cite this

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abstract = "Novel therapeutic strategies for Alzheimer's disease (AD) are of the greatest priority given the consistent failure of recent clinical trials focused on Aβ or pTau. Earlier, we demonstrated that mild mitochondrial complex I inhibitor CP2 blocks neurodegeneration and cognitive decline in multiple mouse models of AD. To evaluate the safety of CP2 in humans, we performed a genome-wide association study (GWAS) using 196 lymphoblastoid cell lines and identified 11 SNP loci and 64 mRNA expression probe sets that potentially associate with CP2 susceptibility. Using primary mouse neurons and pharmacokinetic study, we show that CP2 is generally safe at a therapeutic dose.",

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AU - Gao, Huanyao

AU - Tripathi, Utkarsh

AU - Trushin, Sergey

AU - Okromelidze, Lela

AU - Pichurin, Nicholas P.

AU - Wei, Lixuan

AU - Zhuang, Yongxian

AU - Wang, Liewei

AU - Trushina, Eugenia

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AB - Novel therapeutic strategies for Alzheimer's disease (AD) are of the greatest priority given the consistent failure of recent clinical trials focused on Aβ or pTau. Earlier, we demonstrated that mild mitochondrial complex I inhibitor CP2 blocks neurodegeneration and cognitive decline in multiple mouse models of AD. To evaluate the safety of CP2 in humans, we performed a genome-wide association study (GWAS) using 196 lymphoblastoid cell lines and identified 11 SNP loci and 64 mRNA expression probe sets that potentially associate with CP2 susceptibility. Using primary mouse neurons and pharmacokinetic study, we show that CP2 is generally safe at a therapeutic dose.

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A genome-wide association study in human lymphoblastoid cells supports safety of mitochondrial complex I inhibitor

Abstract

Keywords

ASJC Scopus subject areas

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