Partial inhibition of mitochondrial complex I attenuates neurodegeneration and restores energy homeostasis and synaptic function in a symptomatic Alzheimer’s mouse model

We performed next-generation RNA sequencing (RNA-seq) using brain tissue from 23 months old non-transgenic (NTG), non-treated and CP2 (mitochondrial complex I inhibitor)-treated APP/PS1 (mouse model of Alzheimer`s disease). By comparing transcriptomic data of NTG and vehicle-treated APP/PS1 mice, we found processes affected by the disease in APP/PS1 such as impaired ATP metabolism, ion transport, nervous system development, synaptic transmission, and inflammation. CP2-treatment in APP/PS1 positively affected genes related to immune system, axonogenesis, dendritic spine morphology, synaptic function, among the others. These data demonstrate that pathways improved by CP2 treatment in APP/PS1 mice comprise major pathways essential for therapeutic efficacy in Alzheimer`s disease. mRNA profiles of 23 months old non-transgenic (NTG) and non-treated and CP2 (mitochondrial complex I inhibitor)-treated APP/PS1 mice were generated by deep sequencing, using Illumina HiSeq 4000 with paired end 101-bp read length.