神经损伤与修复
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Figure 1｜Representative images of the Aβ oligomer-induced activation of NMDAR through insertion of the oligomers in the lipid bilayer and its consequent destabilization, sensed by the NMDAR due to their mechanosensitivity.
Mechanical activation of NMDAR: To verify the hypothesis that oligomers may change the physical properties of the cell membrane as a consequence of their interaction with the bilayer and this change results in NMDAR activation, we added specific compounds to the cell membrane known to cause its stretching or compression, to observe variation in the influx of Ca2+ (Fani et al., 2021). In particular, we enriched the cellular membrane with two different lipids: lysophosphatidylcholine, with a “cone” shape characterized by a big polar head, which causes a compression of the phospholipid bilayer inhibiting NMDAR, and arachidonic acid, which has the shape of an “inverted cone” with a small polar head, and has the ability to cause a stretch of the lipid bilayer, with the consequent opening of the receptors without acting as a specific ligand (Casado and Ascher, 1998). We observed the ability of lysophosphatidylcholine to neutralize the oligomer-induced activation of the NMDAR (Figure 1), suggesting that the opposing force exerted by the lipids effectively inhibits the mechanical signal generated by the action of the oligomers onto the bilayer, changing the membrane tension energetically transmitted to the receptors (Fani et al., 2021). By contrast, arachidonic acid, which themselves determines the passage of Ca2+ through the NMDAR, did not have an additive effect with the oligomers (Figure 1), suggesting the same mechanism of action by a membrane stretch induction operates (Fani et al., 2021).