β-Site amyloid precursor protein-cleaving enzyme 1 (BACE1) - the neuronal β-secretase responsible for producing β-amyloid (Aβ) peptides - emerged as one of the key therapeutic targets of Alzheimer's disease (AD). Although complete ablation of the BACE1 gene prevents Aβ formation, we reported that BACE1 knock-out mice display severe presynaptic deficits at mossy fiber (MF)-to-CA3 synapses in the hippocampus, a major locus of BACE1 expression. We also found that the deficits are likely due to abnormal presynaptic Ca2+ regulation. Cholinergic system has been implicated in AD, in some cases involving Ca2+-permeable α7-nicotinic acetylcholine receptors (nAChRs). Here we report that brief application of nicotine, via α7-nAChRs, can restore MF long-term potentiation in BACE1 knock-outs. Our data suggest that activating α7-nAChRs can recover the presynaptic deficits in BACE1 knock-outs.
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