Evaluation of the Therapeutic Effect of Lycoramine on Alzheimer's Disease in Mouse Model.

BACKGROUND Alzheimer's disease is one of the leading health problems characterized by the accumulation of Aβ and hyperphosphorylated tau that accounts for the senile plaque formations causing extensive cognitive decline. Many of the clinical diagnostics of Alzheimer's disease were made in the late stages where the pathological changes had already progressed. OBJECTIVE The objective of this study is to evaluate the promising therapeutic effects of the natural compound lycoramine. The literature reports lycoramine's therapeutic potential in several studies. Other publications show its mechanism of action on the molecular level via label-free differential protein expression analysis. METHOD Lycoramine and galantamine, an FDA approved drug used in treatment of the mild to moderate AD, were administered to 12 month-old 5xFAD mice. Effects of the compounds were investigated by Morris water maze, immunohistochemistry and label-free differential protein expression analyses. RESULTS Here we demonstrated the reversal of cognitive decline via behavioral testing and the clearance of Aβ plaques. Proteomics analysis provided in-depth information on the statistically significant protein perturbations in the cortex, hippocampus and cerebellum sections to hypothesize the possible clearance mechanisms of the plaque formation and the molecular mechanism of the reversal of the cognitive decline in a transgenic mouse model. Bioinformatics analyses showed altered molecular pathways that can be linked with the reversal of cognitive decline observed after lycoramine administration but not with galantamine. CONCLUSION Lycoramine shows therapeutic potential to halt and reverse cognitive decline at the late stages of disease progression, and holds great promise for the treatment of Alzheimer's disease.