Research Field
Dr. Knafo’s Molecular Cognition Laboratory is particularly interested in the molecular and cellular basis of diverse cognitive conditions, and the lab’s researchers analyze the mechanisms leading to cognitive impairment and accordingly develop new compounds capable of enhancing cognitive performance. Dr. Knafo and her team study the mechanisms of action and the effects on synaptic function and performance in a variety of tasks. For example, FGL is a peptide derived from the neural cell adhesion molecule which improves cognition by the activation of the PKC pathway that triggers an activity-dependent delivery of AMPA receptors to the synapses.
This peptide enhances learning and memory in rodents and represents a prototype for the development of other drugs with similar activity. Another prototype drug for developing cognitive enhancers is the PTD4-PI3KAc peptide which, by activating the PI3K signaling pathway, promotes synapse and spine formation and enhances hippocampal dependent memory. Recently the Knafo lab developed a new peptide derived from the well-known tumor suppressor PTEN that prevents pathological interactions between PTEN and PDZ proteins at synapses during exposure to amyloid beta.
This action prevents memory deterioration in a mouse model of Alzheimer’s disease. As a multidisciplinary laboratory, the researchers’ experience in different scientific disciplines (medicine, animal behavior, electrophysiology, molecular biology, morphology) allows them to use a multidisciplinary approach that is an asset in modern neuroscience research.
Dr. Shira Knafo, MD, PhD
In her laboratory, Dr. Knafo seeks to identify the molecular and synaptic mechanisms underlying learning and memory, cognitive malfunction, and cognitive enhancement. This knowledge is further translated to developing novel approaches for memory enhancement.
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Publications
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Sánchez-Puelles, C. et al. (2020)
PTEN Activity Defines an Axis for Plasticity at Cortico-Amygdala Synapses and Influences Social Behavior.
Cerebral cortex, 30(2), pp. 505–524. doi: 10.1093/cercor/bhz103.
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Knafo S. et al. (2016)
PTEN recruitment controls synaptic and cognitive function in Alzheimer's models.
Nat. Neurosci. 19:443-453.
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Knafo S. et al. (2012)
Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement.
PLoS Biol. 10, e1001262.
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Jurado S. and Knafo S. (2012)
Microscale AMPAR reorganization and dynamics of the postsynaptic density.
The Journal of neuroscience 32:7103-7105.
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Jurado S., Benoist M., Lario A., Knafo S., Petrok C.N., Esteban J.A. (2010)
PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.
EMBO J. 29:2827-2840.
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Arendt K.L., Royo M., Fernandez-Monreal M., Knafo S., Petrok C.N., Martens J.R., Esteban J.A. (2010)
PIP3 controls synaptic function by maintaining AMPA receptor clustering at the postsynaptic membrane.
Nat. Neurosci. 13:36-44.
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