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Third, the APP/PS1 transgenic mouse model of Alzheimers disease used in Sun 2021 to test Dihexa in an amyloid-pathology model, with Morris water maze, neuroinflammatory cytokines, and PI3K/AKT pathway activation as primary readouts

Furthermore, TGF-1 induces Smad2/3 phosphorylation through activation of Smad1/5/9, thereby inhibiting the TGF signaling pathway [68]

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Elevated HMGB1 levels have been detected in the blood of patients, where it interacts with receptors such as RAGE and TLR4, forming complexes with IL-1 or LPS to activate proinflammatory signaling pathways (Shimizu et al., 2017)