Type 2 diabetes (T2D) is a metabolic disease, whose incidence is reaching epidemic proportions, with major health consequences. Accumulating evidence demonstrates that T2D increases the risk of dementia, namely Alzheimer’s disease (AD). In this project, we propose to decipher the therapeutic potential of Zinc finger-like protein that regulates apoptosis (Zfra 1-31), a specific WWOX inhibitor, against T2D progression and its associated brain damage. To prove our hypothesis, we will perform studies in high calorie diet-induced diabetic mice treated (or not; control group) with Zfra 1-31. The efficacy of Zfra1-31 will be dissected through the evaluation of several parameters namely, behavior and cognition, WWOX activation and its signaling pathways, including its interaction with mitochondria (known to interact with activated WWOX to induce apoptosis), synaptic integrity and AD-related neurotoxic protein levels. With this project we expect to demonstrate that Zfra 1-31 is a strong therapeutic candidate against T2D-associated neurodegeneration and, its administration in early stages of the disease will avoid the progression/worsening of this complication. This project will bring new therapeutic perspectives for T2D-associated complications, namely brain damage.
The main goal of the project is to explore the therapeutic potential of Zfra 1-31 in preventing or reducing T2D-associated brain damage.
ESCI EXPLORATORY RESEARCH GRANTS