1. Academic Validation
  2. Memantine inhibits β-amyloid aggregation and disassembles preformed β-amyloid aggregates

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

  • Biochem Biophys Res Commun. 2017 Nov 4;493(1):158-163. doi: 10.1016/j.bbrc.2017.09.058.
Kaori Takahashi-Ito 1 Mitsuhiro Makino 2 Keiko Okado 3 Taisuke Tomita 4
Affiliations

Affiliations

  • 1 Venture Science Laboratories, R&D Division, Daiichi-Sankyo Co. Ltd., Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: takahashi.kaori.ne@daiichisankyo.co.jp.
  • 2 Venture Science Laboratories, R&D Division, Daiichi-Sankyo Co. Ltd., Shinagawa-ku, Tokyo 140-8710, Japan.
  • 3 Discovery Science and Technology Department, Daiichi-Sankyo RD Novare Co. Ltd., Tokyo 134-8630, Japan.
  • 4 Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Abstract

Memantine, an uncompetitive glutamatergic N-methyl-d-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 β-amyloid (Aβ) and soluble Aβ oligomers in animal models of AD. The mechanisms by which memantine reduces Aβ levels in the brain were evaluated by determining the effect of memantine on Aβ aggregation using thioflavin T and transmission electron microscopy. Memantine inhibited the formation of Aβ(1-42) aggregates in a concentration-dependent manner, whereas amantadine, a structurally similar compound, did not affect Aβ aggregation at the same concentrations. Furthermore, memantine inhibited the formation of different types of Aβ aggregates, including Aβs carrying familial AD mutations, and disaggregated preformed Aβ(1-42) fibrils. These results suggest that the inhibition of Aβ aggregation and induction of Aβ disaggregation may be involved in the mechanisms by which memantine reduces Aβ deposition in the brain.

Keywords

Alzheimer's disease; Aβ aggregation; Memantine; β-amyloid.

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