| First Author | Knafo S | Year | 2016 |
| Journal | Nat Neurosci | Volume | 19 |
| Issue | 3 | Pages | 443-53 |
| PubMed ID | 26780512 | Mgi Jnum | J:234430 |
| Mgi Id | MGI:5790007 | Doi | 10.1038/nn.4225 |
| Citation | Knafo S, et al. (2016) PTEN recruitment controls synaptic and cognitive function in Alzheimer's models. Nat Neurosci 19(3):443-53 |
| abstractText | Dyshomeostasis of amyloid-beta peptide (Abeta) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Abeta 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 Abeta-induced depression. Mechanistically, Abeta 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 Abeta-induced synaptic toxicity and cognitive dysfunction. Our results provide fundamental information on the molecular mechanisms of Abeta-induced synaptic malfunction and may offer new mechanism-based therapeutic targets to counteract downstream Abeta signaling. |
