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Figure 3 | Molecular Neurodegeneration

Figure 3

From: BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer’s disease

Figure 3

Disturbed calcium homeostasis mediates Aβ-induced BACE1 transcriptional activation. Aβ peptides increase cytoplasmic calcium by at least three mechanisms: stimulation of membrane ion channels or receptors; permeabilization of the membrane; and deregulation of internal calcium channels. Presenilins mutations contribute to the latter. Increased calcium then activates the calpain/cdk5/STAT3 pathway and NFAT1. The transcription factors STAT3 and NFAT1 upregulate BACE1, which then produces more Aβ peptides and a positive feedback mechanism is set up. Aβ, amyloid peptide; BACE1, β-secretase βAPP cleaving enzyme 1; cdk5, cyclin-dependent kinase 5; IP3, inositol 1,4,5-triphosphate; NFAT1, nuclear factor of activated T-cells 1; SERCA, sarco endoplasmic reticulum calcium ATPase; STAT, signal transducer and activator of transcription.

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Molecular Neurodegeneration

ISSN: 1750-1326