New therapeutic strategies for Alzheimer's disease: induction of neural plasticity and mitochondria bolstering by the Rho GTPases' activator CNF1

In the present project, we aim at studying whether CNF1: 1. improves learning and memory in APOE4 TR and APOE3 TR under normal and special diets; 2. improves anxiety-like behavior, since anxiety is most common among AD patients with an age at onset under age 65; 3. promotes remodeling of dendritic spines and dendrite arborisation; 4. stimulates expression and activity of signaling molecules including actin-regulatory proteins, dendrite and dendritic spine associated proteins, scaffolding proteins, ionotropic and metabotropic glutamate receptors; 5. counteracts the defects in the organization, distribution and functionality of AD mitochondria. Finally, in collaboration with the John R. Murphy’s group, we aim at developing and testing active small CNF1 fragments. In fact, the large size of CNF1 implies its delivery through intracerebroventricular (icv) injections, thus rendering its use for therapeutic purposes too invasive. The intraperitoneal (ip) route of administration of a CNF1 derivative able of crossing the blood-brain barrier might thus be extremely advantageous.