Intromitochondrial IκB/NF-κB signaling pathway is involved in amyloid β peptide-induced mitochondrial dysfunction

Mitochondrial dysfunction is a hallmark of amyloid beta peptide (A beta)-induced neuronal toxicity in Alzheimer's disease (AD). However, the underlying mechanism (s) of A beta-induced mitochondrial dysfunction is still not fully understood. There is evidence that nuclear factor-kappa B (NF-kappa B) is involved in A beta-induced neurotoxicity and is present in mitochondria. Using HT22 murine hippocampal neuronal cells and isolated mitochondria, the present study investigated whether intramitochondrial inhibitor of NF-kappa B (I kappa B)/NF-kappa B signaling pathway was involved in mitochondrial dysfunction induced by A beta. It was found that A beta impaired mitochondrial function through a NF-kappa B-dependent signaling pathway. Intramitochondrial I kappa B alpha/NF-kappa B pathway, induced by A beta, decreased the expression of cytochrome c oxidase subunit (COXIII) and inhibited COX activity. These results provide new insights into the mechanism underlying the neurotoxic effect of A beta and open up new therapeutic perspectives for AD.