A new paper, published in Nature Neuroscience, reports that in Alzheimer’s disease, synaptic plasticity is altered by a protein originally described as a tumor suppressor: PTEN. In 2010, the research group of Dr. Esteban discovered that PTEN is recruited to synapses during normal (physiological) synaptic plasticity. This new investigation by Drs. Knafo, Venero and Esteban, now indicates that this mechanism runs uncontrolled during Alzheimer’s disease. One of the pathological agents of the disease, the beta-amyloid, drives PTEN into synapses excessively, unbalancing the mechanisms for synaptic plasticity and impairing memory formation.
An important aspect of this study is that it also describes how PTEN is recruited to synapses in response to beta-amyloid, and proposes a strategy to prevent it from occuring. Using a mouse model of Alzheimer’s disease, the investigators developed a molecular tool to shield synapses from the recruitment of PTEN. With this tool, neurons are rendered resistant to beta-amyloid, and Alzheimer’s mice preserve their memory.
Journal Reference:
- Shira Knafo, Cristina Sánchez-Puelles, Ernest Palomer, Igotz Delgado, Jonathan E Draffin, Janire Mingo, Tina Wahle, Kanwardeep Kaleka, Liping Mou, Inmaculada Pereda-Perez, Edvin Klosi, Erik B Faber, Heidi M Chapman, Laura Lozano-Montes, Ana Ortega-Molina, Lara Ordóñez-Gutiérrez, Francisco Wandosell, Jose Viña, Carlos G Dotti, Randy A Hall, Rafael Pulido, Nashaat Z Gerges, Andrew M Chan, Mark R Spaller, Manuel Serrano, César Venero, José A Esteban. PTEN recruitment controls synaptic and cognitive function in Alzheimer's models. Nature Neuroscience, 2016; 19, 443-453, DOI: 10.1038/nn.4225