RT Journal Article
T1 PTEN recruitment controls synaptic and cognitive function in Alzheimer's models
A1 Knafo, Shira
A1 Pereda Pérez, María Inmaculada
A1 Ordóñez Gutiérrez, Lara
A1 Serrano Ríos, Manuel
A1 Esteban, José A
AB 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.
PB Nature Research
SN 1097-6256
SN 1546-1726
YR 2016
FD 2016-01-18
LK https://hdl.handle.net/20.500.14352/114277
UL https://hdl.handle.net/20.500.14352/114277
LA eng
NO 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
DS Docta Complutense
RD 23 abr 2025