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

• Published in: Biochemical and biophysical research communications Vol. 493; no. 1; pp. 158 - 163
• Main Authors: Takahashi-Ito, Kaori, Makino, Mitsuhiro, Okado, Keiko, Tomita, Taisuke
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.11.2017
• Subjects: Alzheimer disease; Alzheimer's disease; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - ultrastructure; animal models; antagonists; Aβ aggregation; brain; Dimerization; drug therapy; Memantine; Memantine - chemistry; mutation; Peptide Fragments - chemistry; Peptide Fragments - ultrastructure; Protein Binding; transmission electron microscopy; β-amyloid; PBS; Aβ; APP; ThT; Memantine; AD; DW; CSF; Aβ aggregation; NMDA; Alzheimer's disease; β-amyloid
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2017.09.058

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. •Memantine has a potential to inhibit the formation of Aβ oligomer and fibrils.•Memantine also has a potential to dissociate the human Aβ aggregates.•Novel beneficial effect of memantine on treatment Alzheimer's disease is proposed.