A novel DSC approach for evaluating protectant drugs efficacy against dementia

Biochim Biophys Acta Mol Basis Dis. 2017 Nov;1863(11):2934-2941. doi: 10.1016/j.bbadis.2017.07.033. Epub 2017 Aug 1.

Abstract

Differential scanning calorimetry was applied to evaluate the efficacy of preventive treatments with biologically active compounds of plant origin against neurodegenerative disorder in mice. As we reported recently, large differences exist between the heat capacity profiles of water-soluble brain proteome fractions from healthy animals and from animals with scopolamine-induced dementia: the profiles for healthy animals displayed well expressed exothermic event peaking at 40-45°C, by few degrees above body temperature, but still preceding in temperature the proteome endothermic denaturational transitions; the low-temperature exotherm was completely abolished by the scopolamine treatment. Here we explored this signature difference in the heat capacity profiles to assess the efficacy of preventive treatments with protectant drugs anticipated to slow down or block progression of dementia (myrtenal, ellagic acid, lipoic acid and their combinations, including also ascorbic acid). We found that these neuroprotectants counteract the scopolamine effect and partially or completely preserve the 'healthy' thermogram, and specifically the low-temperature exotherm. These results well correlate with the changes in the cognitive functions of the animals assessed using the Step Through Test for learning and memory. The exothermic event is deemed to be associated with a reversible process of fibrillization and/or aggregation of specific water-soluble brain protein fractions preceding their denaturation. Most importantly, the results demonstrate that the effect of scopolamine and its prevention by protectant substances are clearly displayed in the heat capacity profiles of the brain proteome, thus identifying DSC as a powerful method in drug testing and discovery.

Keywords: Alzheimer's disease; Ellagic acid; Intrinsically disordered proteins; Lipoic acid; Myrtenal; Neuroprotectant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognition / drug effects*
  • Dementia / metabolism
  • Dementia / pathology
  • Dementia / prevention & control*
  • Drug Evaluation, Preclinical
  • Male
  • Mice
  • Mice, Inbred ICR
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Proteome / metabolism*
  • Scopolamine / adverse effects
  • Scopolamine / pharmacology

Substances

  • Neuroprotective Agents
  • Proteome
  • Scopolamine