IKKβ Alleviates Neuron Injury in Alzheimer's Disease via Regulating Autophagy and RIPK1-Mediated Necroptosis.

Alzheimer's disease (AD), featured with memory loss and multiple cognitive impairments, is a devastating neurodegenerative disease that affects millions of people in the world, especially the elder people. IKKβ plays important role in the development of neurodegenerative diseases. However, the molecular mechanism of IKKβ, especially related with autophagy and necroptosis, in AD, is still unclear. Here, we studied the function of IKKβ in regulating autophagy and RIPK1-induced necroptosis in SH-SY5Y cells and APP/PS1 mice. By silencing IKKβ in the SH-SY5Y cells, we found that inhibition of IKKβ could promote the RIPK1-induced necroptosis caused by Aβ accumulation as well as suppress the autophagy of SH-SY5Y cells. Furthermore, we discovered that autophagy was significantly enhanced, and RIPK1-induced necroptosis was inhibited when IKKβ was constitutively activated in SH-SY5Y cells. Then, using APP/PS1 mouse model, we demonstrated that silencing IKKβ could significantly enhance the accumulation of Aβ but have not impact on the mice behavior and cognitive ability. Even the controversial results about the role of IKKβ in AD is not fully understood, our results might provide an important potential therapeutic target for slowing AD. .