TMEM16B (ANO2) is the Ca2+-activated chloride channel expressed in multiple brain regions, including the hippocampus. Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is characterized by cognitive decline and synaptic plasticity impairment. We found that TMEM16B was highly expressed in hippocampus, and it was down-regulating in 5xFAD mice and Aβ1-42-treated sh-sy5y cells. And down-regulating TMEM16B could induce Sh-sy5y cell death. It is shown that up-regulating TMEM16B could reduce cell death and cell apoptosis induced by Aβ1-42 in Sh-sy5y cell. Furthermore, we overexpressed TMEM16B via infusion lentivirus into the bilateral hippocampus, which was sufficient to eliminate cognitive dysfunctions and synaptic plasticity damage. Moreover, increasing TMEM16B activated the shutter protein CaMKⅡ in 5xFAD mice implying that the improvement for AD-like pathology of TMEM16B expression were associated with modifying CaMKⅡ pathway. These findings suggest that TMEM16B is an essential regulator of hippocampus-dependent learning and memory, which can be an ideal target for the development of AD in the future.

TMEM16B,Alzheimer’s disease,Hippocampus,Synaptic plasticity,Cognitive dysfunctions