Therapeutic potential of Simvastatin and Doxycycline combination for Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder resulting from Amyloid β (Aβ) accumulation. It leads to a decrease in memory and an increase in the production of reactive oxygen species and reactive nitrogen species and also increases Tubulin associated unit phosphorylation. During AD, the cholesterol levels in the brain increase, and these regions are called lipid rafts. These lipid rafts are hosts for β and γ secretases. As a result, mono fibrils develop, which lead to Aβ oligomerization and, eventually, Aβ accumulation. Hence, the present study was designed to evaluate the protective effect of Simvastatin (cholesterol synthesis inhibitor) and Doxycycline (anti-amyloidogenic drug) for Aβ clearance in Aβ-induced AD model, in female C57BL/6 mice. The mice were evaluated for spatial memory and olfactory sensation using the Morris water maze and Buried pellet test, respectively. The group treated with the combination of Simvastatin and Doxycycline at two different concentrations showed a recovery of memory and olfactory sensation when compared to the control group. The results have shown that the high-dose combination of Simvastatin and Doxycycline exhibits cholesterol lowering property by blocking the 3-hydroxy-3-methylglutaryl coenzyme A reductase pathway, thereby regulating cholesterol, and eventually resulting in anti-Alzheimer’s activity.