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bioRxiv · 10.1101/593202

Induction of p73, Δ133p53, Δ160p53, pAKT leads to neuroprotection via DNA repair by 5-LOX inhibition

Shekhar, S.·Dey, S.
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Abstract

Lipooxygenase-5 (5-LOX), protein is involved in the pathologic phenotype of AD which includes amyloid-plague and tau hyperphosphorylation. This study aims to identify the mechanistic role in neuroprotection by peptide YWCS, the 5-LOX inhibitor in neurotoxic SH-SY5Y cell line developed by the treatment of A{beta}25-35. The cells were treated with A{beta}25-35 and with different doses of YWCS. The effect on cell survival pathways were determined by western blot using polyclonal anti body of p53, anti-Akt and anti-phosphorylated-Akt. Immunoprecipitation and mass spectroscopic studies were done to identify the altered proteins. Over expression of phosphorylated-Akt and 3 bands of p53 isoforms were observed which correspond to p73, {Delta}133p53 and {Delta}160p53 in the cells treated only with 80{micro}M of YWCS compare to untreated cells. However, no alteration of total p53 and Akt were observed. The results exposed the novel mechanistic pathway of neuroprotection by 5-LOX inhibition, which is likely to be mediated by DNA DSB repair through p53 isoforms and PI3K/Akt pathway. Our finding has opened a new window in the therapeutic approach for the prevention of AD.

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Shekhar, S., Dey, S.. 2019-03-29. Induction of p73, Δ133p53, Δ160p53, pAKT leads to neuroprotection via DNA repair by 5-LOX inhibition. https://doi.org/10.1101/593202

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