Changes in cell structure and biochemistry, formation of senile plaques and neurofibrillary tangles are common features of the brain in degenerative process. These neurofibrillary tangles are consisted essentially of hyperphosphorylated tau protein. The presence of these protein aggregates leads to intracellular damage culminating in cell death. Failure in the process of cellular degradation could favor the aggregation of intracellular and extracellular proteins and culminate in neurodegeneration. For this reason, we intend to analyze the formation of autophagolysosomes and the colocalization of autophagosomes with hyperphosphorylated tau and alpha-synuclein, in order to study the relation between autophagy and protein aggregation. For this analysis, specific antibodies will be used to detect hyperphosphorylated tau and alpha-synuclein. The analysis of autophagolysosomes will be performed using fluorescent probes which mark acidic organelles with different colors depending upon the pH range. This study will be performed on primary cell cultures of the hippocampus, substantia nigra and locus coeruleus subjected to rotenone exposure in concentrations from 0.3 to 1nM, considering that 1nM is able to induce aggregates containing hyperphosphorylated tau protein and alpha-synuclein in the cells.
News published in Agência FAPESP Newsletter about the scholarship: