TRP channels and Alzheimer´s disease: a molecular study
Alzheimer's disease (AD) is a neurodegenerative disease in which temperature has been described as an important factor for the development of the sporadical form of the disease. There are two histopathological markers of the disease, senile plaques of beta amyloid protein, and neurofibrillary tangles formed by the hyperphosphorylated tau protein. The tau protein is found in neurons in two different forms, phosphorylated and dephosphorylated, whose dynamics are regulated by enzymes kinases and phosphatases. Functionally, the tau protein promotes the polymerization and stabilization of the cell structure through its association with microtubules in dephosphorylated form. Studies indicate that subneutral temperatures lead to increased phosphorylation of the tau protein, but the mechanisms involved in the transduction of this thermal signal to cells are not yet known. In this sense, TRP channels may be the key to the signaling mechanism for the increase in tau hyperphosphorylation. TRPV4 channels are widely expressed in the central nervous system, with a thermal activation range between 27 and 34ºC, a thermal range that is also conducive to increased phosphorylation of the tau protein and can also be activated in pathological conditions. Therefore, this work was carried out with the objective of investigating the participation of TRPV4 channels in the hyperphosphorylation process of tau protein induced by drop in temperature in PC12 cell culture. For that, the cells were submitted to a temperature of 33 and 37ºC and treated with TRPV4 agonist and antagonist. The results obtained so far have shown that the temperatures used do not alter the viability of the experimental model, nor does the blocking and chemical activation of TRPV4 channels cause changes in cell viability. Regarding proteins, there were also no significant differences in the levels of expression of TRPV4 proteins and phosphorylated tau regardless of the conditions that the cells were subjected to.