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Mini‐review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility
Author(s) -
Curtis David,
Bandyopadhyay Sreejan
Publication year - 2021
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12410
Subject(s) - protein tyrosine phosphatase , pi3k/akt/mtor pathway , phosphorylation , tyrosine , protein kinase b , phosphatase , tyrosine phosphorylation , biology , pathogenesis , alzheimer's disease , cancer research , disease , signal transduction , genetics , biochemistry , medicine , immunology
A variety of findings from in vitro experiments and animal models support the hypothesis that one contribution to pathogenesis in Alzheimer's disease (AD) is enhanced phosphorylation of tau protein, which may be triggered by amyloid β (Aβ) and mediated by impaired activity of the PI3K/Akt signaling pathway. A number of tyrosine phosphatases act to reduce PI3K/Akt activity, and inhibition of tyrosine phosphatases is protective against Aβ toxicity in cell cultures and whole animals. Results from analysis of exome sequenced late onset AD cases and controls similarly show that rare coding variants predicted to damage PI3K functioning increase AD risk, whereas those which are predicted to damage genes for tyrosine phosphatase genes are protective. Taken together, these results support the proposition that tyrosine phosphatase antagonists might be trialed as therapeutic agents to protect against the development of AD.