Evaluation of the effects of the cannabinoid agonist win- 55212-2 in the cell model of klotho deletion.

Abstract

Klotho, a protein encoded by the human KL gene which regulates several physiological processes such as phosphate, calcium and vitamin metabolism. It is known as an aging suppressor protein due to the increased expression associated with increased lifespan. On the other hand, it was demonstrated in literature that Klotho gene deficiency in mouse generates cognitive impairment, oxidative stress and an imbalance in glutamatergic signaling similarly to what is observed in neurodegenerative diseases. And considering that the neuromodulation function of Klotho extends to the promotion and maintenance of neurogenesis, neural stem cells of protein klotho knockout mouses sufferss changes in programming, progression, and dendritic arborization formation. Understanding and promoting the neurogenesis process is a possible tool to delay aging and the progression of neurodegenerative diseases. Currently, there is a great demand for research into therapeutic agents in neurodegenerative diseases. In this context, the literature had demonstrated that endogenous and exogenous cannabinoids are potential anti-inflammatory, immunomodulatory and neuroprotective agents. The cannabinoid agonist WIN - 2 have a several neuroprotective role in different models. Therefore, this project will assess whether the WIN55212-2 project is capable of reversing possible changes proliferation, differentiation and glutamatergic signaling of stem neural cells induced by the Klotho gene hypofunction.