Zhang C, Wu B, Beglopoulos V, Wines-Samuelson M, Zhang D, Dragatsis I, Südhof TC, Shen J.
Presenilins are essential for regulating neurotransmitter release.
Nature. 2009 Jul 30;460(7255)
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Another example that loss of function of APP is likely the basic mechanism of neurodegeneration.
Dr. Saura discussed that FAD presenilin mutation showed neurodegeneration in humans, but not in mice. Why this difference? We believe that homocysteic acid (HA) may be a pathogenic compound for Alzheimer disease. In our hands, HA induced neurodegeneration. We found recently that there is a big difference in urinary HA excretion between humans and mice. Human HA excretion into urine is 1,000 times higher than in mice. From our observation, humans show more severe HA-induced neurodegeneration than do mice, and HA production is related to presenilin activation (submitted for publication).