Biochemical and Biophysical Research Communications, Vol.493, No.1, 158-163, 2017
Memantine inhibits beta-amyloid aggregation and disassembles preformed beta-amyloid aggregates
Memantine, an uncompetitive glutamatergic N-methyl-o-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD). We previously reported that chronic treatment of AD with memantine reduces the amount of insoluble beta-amyloid (All) and soluble A beta oligomers in animal models of AD. The mechanisms by which memantine reduces A beta levels in the brain were evaluated by determining the effect of memantine on All aggregation using thioflavin T and transmission electron microscopy. Memantine inhibited the formation of A beta(1-42) aggregates in a concentration-dependent manner, whereas amantadine, a structurally similar compound, did not affect A beta aggregation at the same concentrations. Furthermore, memantine inhibited the formation of different types of AP aggregates, including Ails carrying familial AD mutations, and disaggregated preformed A beta(1-42) fibrils. These results suggest that the inhibition of A beta aggregation and induction of AP disaggregation may be involved in the mechanisms by which memantine reduces All deposition in the brain. (C) 2017 Elsevier Inc. All rights reserved.