Memantine inhibits beta-amyloid aggregation and disassembles preformed beta-amyloid aggregates

作者：Takahashi Ito Kaori^*; Makino Mitsuhiro; Okado Keiko; Tomita Taisuke

来源：Biochemical and Biophysical Research Communications, 2017, 493(1): 158-163.

DOI：10.1016/j.bbrc.2017.09.058

• Memantine
• beta-amyloid
• A beta aggregation
• Alzheimer's disease

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.

• 出版日期2017-11-4