Knafo, ShiraPereda Pérez, María InmaculadaOrdóñez Gutiérrez, LaraSerrano Ríos, ManuelEsteban, José A2025-01-142025-01-142016-01-18Knafo, 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.42251097-62561546-172610.1038/nn.4225https://hdl.handle.net/20.500.14352/114277Dyshomeostasis 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.engjournal article10.1038/NN.4225https://www.nature.com/articles/nn.4225restricted access616.894-053.9Neurociencias (Medicina)2490 Neurociencias