PI3K Mediates Stretch-Induced COX-2 Expression During Urinary Tract Obstruction

Owusu-Ofori, Kwadwo; Learned, Meghan K; Mellon, William S.; Nakada, Stephen Y.

doi:10.1089/end.2012.0252

Cited by 1 publication

(1 citation statement)

References 24 publications

(19 reference statements)

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“…To evaluate the effect of rapamycin and genetic deletion of PI3Kγ, the following groups were used: PBS + vehicle, Aβ + vehicle, Aβ + rapamycin 5 mg/kg, Aβ in PI3Kγ −/− mice. The doses of LY294002 and rapamycin were chosen based on previous published data 67 68 69 70 71 .…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective effects of the anticancer drug NVP-BEZ235 (dactolisib) on amyloid-β 1–42 induced neurotoxicity and memory impairment

Bellozi

Lima

Doria

et al. 2016

Sci Rep

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the main cause of dementia. Substantial evidences indicate that there is over-activation of the PI3K/Akt/mTOR axis in AD. Therefore, the aim of the present study was to investigate the effects of NVP-BEZ235 (BEZ; dactolisib), a dual PI3K/mTOR inhibitor that is under phase I/II clinical trials for the treatment of some types of cancer, in hippocampal neuronal cultures stimulated with amyloid-β (Aβ) 1–42 and in mice injected with Aβ 1–42 in the hippocampus. In cell cultures, BEZ reduced neuronal death induced by Aβ. BEZ, but not rapamycin, a mTOR inhibitor, or LY294002, a PI3K inhibitor that also inhibits mTOR, reduced the memory impairment induced by Aβ. The effect induced by Aβ was also prevented in PI3Kγ−/− mice. Neuronal death and microgliosis induced by Aβ were reduced by BEZ. In addition, the compound increased IL-10 and TNF-α levels in the hippocampus. Finally, BEZ did not change the phosphorylation of Akt and p70s6K, suggesting that the involvement of PI3K and mTOR in the effects induced by BEZ remains controversial. Therefore, BEZ represents a potential strategy to prevent the pathological outcomes induced by Aβ and should be investigated in other models of neurodegenerative conditions.

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Section: Methodsmentioning

confidence: 99%