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. 2021 Sep 29;10(10):2591. doi: 10.3390/cells10102591

Figure 3.

Figure 3

Proposed feedback modulation of Aβ synthesized from APP by the enzyme γ-secretase. Two main lipid groups, cholesterol and sphingomyelin, are closely related to Aβ production in AD. Cholesterol increases γ-secretase activity, which leads to elevated Aβ production. Conversely, Aβ downregulates cholesterol de novo synthesis from acetyl-CoA by inhibiting enzyme HMG-CoA reductase. Sphingomyelin inhibits γ-secretase activity, and in return reduced γ-secretase activity depresses sphingomyelin synthase activity. (Figure modified from the manuscript Zinser E.G. et al. BBA 2007;1768:1991–2001.) The related lipid species we measured are listed in the parentheses. Acetyl-CoA synthesized from fatty acids is released from diacylglycerol and triacylglycerols. Abbreviations: APP, amyloid precursor protein; CE, cholesteryl esters; CER, ceramides; DAG, diacylglycerols; DCER, dihydroceramides; HCER, hexosylceramides; LCER, lactosylceramides; SM, sphingomyelins; TAG, triacylglycerols.