Hypothetic model of the physiological functions of Aβ and AICD in the regulation of GD3-synthase (GD3S) – the enzyme controlling major brain ganglioside composition.
<p>(<i>A</i>) Amyloidogenic proteolytic processing of the Alzheimer's amyloid precursor protein (APP) releases amyloid-beta peptides (Aβ) and the intracellular domain of APP (AICD). Aβ and AICD inhibit GD3S, resulting in reduced conversion of <i>a</i>- to <i>b</i>-series gangliosides. As a consequence of reduced conversion of <i>a</i>- to <i>b</i>-series gangliosides, GM3 increases whereas GD3 decreases. In return, both gangliosides, GM3 and GD3, themselves regulate the proteolytic cleavage of APP. The <i>b</i>-series ganglioside GD3 increases, whereas the <i>a</i>-series gangliosides GM3 decreases amyloidogenic proteolytic processing of APP.</p
