BDNF and Alzheimer disease: SIRT3 has emerged as a key regulator of mammalian transcription in response to cellular metabolic state and stress.754 Recent studies have shown that SIRT3 dysfunction leads to mitochondrial and neuronal damage in AD, suggesting that SIRT3 has a protective role in hippocampal neurons.755 Intermittent food deprivation also reduces neuronal network hyperexcitability and ameliorates deficits in hippocampal synaptic plasticity in a SIRT3-dependent manner in animal models of AD.756 Pituitary adenylate cyclase activating polypeptide, a neurotrophin, stimulates mitochondrial SIRT3 production.