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Mini-review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility

Curtis, D; Bandyopadhyay, S; (2021) Mini-review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility. Annals of Human Genetics , 85 (1) pp. 1-6. 10.1111/ahg.12410. Green open access

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Abstract

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.

Type: Article
Title: Mini-review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/ahg.12410
Publisher version: https://doi.org/10.1111/ahg.12410
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Akt, Alzheimer's disease, PI3K, tau protein, tyrosine phosphatase
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10128868
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