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Fig. 3 | Alzheimer's Research & Therapy

Fig. 3

From: The pleiotropic role of p53 in functional/dysfunctional neurons: focus on pathogenesis and diagnosis of Alzheimer’s disease

Fig. 3

The unfolded p53 protein underlies various early hallmarks of AD pathology. Sublethal Aβ concentrations inhibit the Zyxin/HIPK2 signaling axis, resulting in upregulation of MT2A. Following MT2A upregulation, zinc atoms are chelated which are necessary to maintain wild-type p53 conformation. In addition, chronic exposure to subtoxic nitrosative stress results in nitration of p53 tyrosine residues, misfolding the p53 protein, and dysregulating its activity. An increase in unfolded p53 protein was directly linked to downregulation of SOD and GAP-43, and to upregulation of CD44 and mTOR, potentially leading to impaired redox homeostasis, synaptic impairment, inflammation, and aberrant cell cycle, respectively. Aβ, amyloid beta; GAP-43, growth-associated protein 43; HIPK2, homeodomain interacting protein kinase 2; MT2A, metallothionein 2A; mTOR, mammalian target of rapamycin; ROS, reactive oxygen species; SOD, superoxide dismutase

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