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. Author manuscript; available in PMC: 2014 Aug 8.
Published in final edited form as: J Alzheimers Dis. 2014;40(1):1–17. doi: 10.3233/JAD-131544

Fig. 1. Intermolecular Effects of HSF and FOXO3 in Non-Pathogenic Aβ Metabolism.

Fig. 1

Schematic representation of interlocking roles for heat shock factors and FOXO3 in Aβ metabolism. Healthy cell. HSF, HSP, and FOXO3 are all at normal expression and activity. A minority of AβPP is processed via the β-secretase pathway, producing Aβ, at least some of which is directed intracellularly for functions such as transcription factor activity. HSF binds to HSP and is activated. Active HSF (*) is directed to the nucleus where it upregulates (among others) HSP expression. HSP activation (HSP90) directs excess intracellular Aβ toward proteasomes, where it is degraded to amino acids (AA). FOXO3, among its multiple functions, catalyzes formation of amyloid plaque from Aβ. In addition, extracellular non-plaque Aβ is cleared by enzymes such as insulin-degrading enzyme (IDE).