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00925njm 22002777a 4500 dc Knafo, Shira author Pereda Pérez, María Inmaculada author Ordóñez Gutiérrez, Lara author Serrano Ríos, Manuel author Esteban, José A author 2016 Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression, rescued normal synaptic function and cognition in cellular and animal models of Alzheimer's disease. Conversely, transgenic mice that overexpressed PTEN displayed synaptic depression that mimicked and occluded Aβ-induced depression. Mechanistically, Aβ triggers a PDZ-dependent recruitment of PTEN into the postsynaptic compartment. Using a PTEN knock-in mouse lacking the PDZ motif, and a cell-permeable interfering peptide, we found that this mechanism is crucial for Aβ-induced synaptic toxicity and cognitive dysfunction. Our results provide fundamental information on the molecular mechanisms of Aβ-induced synaptic malfunction and may offer new mechanism-based therapeutic targets to counteract downstream Aβ signaling. Knafo, Shira, et al. «PTEN Recruitment Controls Synaptic and Cognitive Function in Alzheimer’s Models». Nature Neuroscience, vol. 19, n.o 3, marzo de 2016, pp. 443-53. https://doi.org/10.1038/nn.4225 1097-6256 10.1038/nn.4225 https://hdl.handle.net/20.500.14352/114277 https://doi.org/10.1038/nn.4225 https://www.nature.com/articles/nn.4225 PTEN recruitment controls synaptic and cognitive function in Alzheimer's models