Work

Corrigendum to “Modulation of mitochondrial complex I activity averts cognitive decline in multiple animal models of familial Alzheimer's disease” [EBioMedicine 2 (2015) 294–305]

Year: 2019

Type: erratum

Abstract: In the version of this article originally published, in Supplementary Tables 1 and 2 CP2 concentrations were incorrectly presented in μM instead of nM. Tables are included here to reflect correct values including additional data for independent concentration evaluation. The mistake was introduced due to an error in the concentration of the standard used for the HPLC quantification. Additionally, in the Results section, the sentence “Average concentration of CP2 in the brain of new-born mice was ~90 μM, and in adult mice ~130 μM …” should be replaced with: “Average concentration of CP2 in the brain of new-born mice was ~90 nM, and in adult mice ~130 nM …”. Since CP2 was used as a model compound for a proof of concept studies, this mistake will not impact any preclinical developments. Download .docx (.02 MB) Help with docx files Supplementary Table 1 Download .docx (.02 MB) Help with docx files Supplementary Table 2 Download .doc (.05 MB) Help with doc files Supplementary Table 3 Download .pdf (7.24 MB) Help with pdf files Supplementary material Modulation of Mitochondrial Complex I Activity Averts Cognitive Decline in Multiple Animal Models of Familial Alzheimer's DiseaseDevelopment of therapeutic strategies to prevent Alzheimer's disease (AD) is of great importance. We show that mild inhibition of mitochondrial complex I with small molecule CP2 reduces levels of amyloid beta and phospho-Tau and averts cognitive decline in three animal models of familial AD. Low-mass molecular dynamics simulations and biochemical studies confirmed that CP2 competes with flavin mononucleotide for binding to the redox center of complex I leading to elevated AMP/ATP ratio and activation of AMP-activated protein kinase in neurons and mouse brain without inducing oxidative damage or inflammation. Full-Text PDF Open Access

Source: EBioMedicine

DOI: 10.1016/j.ebiom.2019.03.062