Editorial Volume 15, Issue 18 pp 9235—9237

Beyond amyloid: altered gene function in neurodegenerative diseases

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Figure 1. Summary of BAD-Glu Phenomenon. Exploring the role of APP and the Swedish mutation in BAD-Glu mechanisms and glutamate release. (A) APP interacts with SV proteins via intraluminal (ISVAID) and cytosolic (JCasp) domains, with opposite effects on glutamate release. BACE1 cleavage of APP can disrupt ISVAID-SV protein interaction and trigger facilitation of JCasp-SV protein interaction, which tune-up SV exocytosis. (B) During fusion of synaptic vesicles to the presynaptic membrane, γ-secretase cleaves βCTF and releases Aβ in the synaptic area. (C) Swedish mutation on BACE1 cleavage site cause an increased BACE1 cleavage and this may promote glutamate release. (D) During SV fusion, the increase in βCTF due to increased BACE1 cleavage may lead to an increase in Aβ release into the synaptic area. Created with https://biorender.com/.