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Figure 5 | Molecular Neurodegeneration

Figure 5

From: Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia

Figure 5

Models explaining how GSI treatment leads to memory deficits. GSI treatment causes accumulation of β-CTF (a) and α-CTF (b). One or both of these APP metabolites may exert a synaptic-toxic activity leading to worsening of memory. This model also suggests that the products of γ-processing of β-CTF and α-CTF (Aβ, the APP intracellular domain AID/AICD, and P3) do not play a major role in the pathogenesis of memory loss. (c) γ-secretase cleaves more than 40 substrates (indicated as GSS). These cleavages release an Aβ/P3 like soluble peptide (GSS-sP) and an intracellular domain peptide (GSS-ICD). The inhibition of γ-cleavage of these other substrates will lead to a reduction in GSS-sP and GSS-ICD and an accumulation of GSS. These changes for one or more of these other GSS may participate in or cause the worsening of memory loss in FDDKI mice.

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