Proteomic Analyses of Exothermic Processes in Rat Brain Homogenate

Abstract

Alzheimer’s disease (AD) is the most widespread neurodegenerative disorder which can be induced by scopolamine, but the underlying molecular mechanism is poorly understood. Recently, differential scanning calorimetry (DSC) has been used to study healthy and scopolamine-treated mice. A well-expressed exothermic transition minimum in the range of 35 - 45°C was determined in the DSC profiles of healthy mice supernatants. To explain this process, using two-dimensional gel electrophoresis (2D-PAGE) coupled with MALDI-TOF-TOF, poorly soluble membrane proteins in hippocampal proteome of rat brain tissue were identified. The different behavior of the hippocampal proteome from the healthy rats before and after heating to 45oC was identified. Due to the demonstrated change in protein level of tau protein and tubulin in the rat hippocampus after heating to 45°C, it was suggested that the observed exothermic process at 35-45°C in rat may be due to the partial unfolding of tau protein, which leads to the release of tubulin. Both proteins together are involved in protein fibrillation and aggregation. Another important result is the discovery of different profiles for the proteome of hippocampal rat homogenates with scopolamine-induced neurodegenerative disorder and its characteristics of healthy rats. The reported results from this study can help clarify the molecular mechanisms of scopolamine-induced dementia and neurodegenerative processes in general.