The neuroprotective effects of progestagens in degenerative processes such as in Alzheimer's disease have been suggested by several studies. The modulation of autophagy is considered a promising strategy for the treatment of tauopathies, such as Alzheimer's disease, which are associated with the accumulation of intracellular aggregates of the hyperphosphorylated tau protein. Studies indicate that progestagens may regulate the autophagic process, but the role of these neuroesteroids needs to be further explored in the central nervous system. Therefore, this project aims to investigate the role of progestagens and its receptors in the modulation of autophagy pathways in a cellular model of tauopathy. For this, it will be used a neuronal cellular model overexpressing the human tau protein (tau 4R or P301L). It will be evaluated the modulation of autophagy by activation/inhibition of the progestagen receptors with selective agonists/antagonists and progestagens-related drugs selected from a compound library screening, in order to search for compounds that are able to reduce the protein accumulation in this experimental model. It will also be studied the intracellular signalling and mitochondrial bioenergetics modulated by activation/inhibition of the progestagens receptors. Considering that progestagens have an important role in neuroprotection, autophagy regulation by the modulation of its receptors may provide new therapeutic alternatives to Alzheimer's disease.
News published in Agência FAPESP Newsletter about the scholarship: