35 2.8: Future Directions

A potential further direction for this subject could be continued experiments with endophilin-1 knockout. The proposed connection in section 2.7 between increased Aβ1-42 oligomers causing increased endophilin-1 expression and decreased AMPA receptors due to endocytosis by endophilin-1, possibly due to clathrin, would be a good future study. These two studies found that increased Aβ1-42 oligomers, respectively, caused an increased in endophilin-1 (Yin et al, 2019) and a decrease in AMPA receptors (Hseih et al, 2006); with both of these events causing synaptic dysfunction. Therefore, by combining endophilin-1 knockout with studying AMPA receptors mutations, this hypothesized interaction could possibly be true. If this was true, it would that endophilin-1 knockout restores function by allowing AMPA receptors to remain on the surface of neurons and continue to send excitatory signals, preventing long-term depression and synaptic dysfunction while increasing long-term potentiation. This, of course, is not a cure for Alzheimer’s disease, but it could help prevent the onset of symptoms and allow someone suffering from Alzheimer’s disease to retain some ability to care for themselves or retain new memories for slightly longer.

A second area of future research is on the other isoforms of endophilin, particularly Endophilin-B. Endophilin B is found to have quite the opposite effect from endophilin A in AD. Like endophilin A, endophilin-B1 is also a multifunctional protein. In a study done by Wang et al., endophilin-B was found to have a protective effect on neurons. In mice models of Alzheimer’s, endophilin-B1 declines with disease progression and negatively correlates with amyloid-β amount. In mice, they found that overexpression of endophilin-B1 protected against the apoptosis pathway induced by amyloid-β. And when endophilin-B1 is deleted, increased synaptic dysfunction and more plagues were observed. Wang et al. suggest a feed-forward mechanism, where amyloid-β decreases endophilin-B1 levels, which leads to plaque buildup and AD pathology. Finding out the function and role of endophilin B in Alzheimer’s can give another option for treating AD. It can be used to counteract the effects caused by amyloid-β to slow AD progression.