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Jean-Noël Octave, Nathalie Pierrot, Susana Ferao Santos, Natalia N. Nalivaeva and Anthony J. Turner From synaptic spines to nuclear signaling: nuclear and synaptic actions of the amyloid precursor protein Journal of Neurochemistry 126

Version of Record online: 3 APR 2013 | DOI: 10.1111/jnc.12239

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So far, no new therapeutic agents for Alzheimer's disease (AD) have reached the clinics based on reducing amyloid β-peptide (Aβ) levels through the use of secretase inhibitors or immunotherapy. Here, we highlight emerging areas of amyloid precursor protein (APP) function that may provide new insights into synaptic development, cognition, and gene regulation. Endogenous APP in primary cortical neurons has a key role in maintaining neuronal calcium homeostasis essential for synaptic transmission. Disruption of this homeostatic mechanism predisposes to aging and AD. The intracellular domain of APP (AICD) is also a key epigenetic regulator of various genes, including APP itself, the amyloid-degrading enzyme neprilysin (NEP), and aquaporin-1.

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