الفهرس 
Pharmacological study of the efficacy of a drug targeting oxidative stress signaling in experimentally-induced Alzheimer’s disease in rats
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Abstract
Receptor tyrosine kinase (RTK) signaling is substantial in learning and memory. The upregulation of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER-2) has been implicated in the pathophysiology of Alzheimer’s disease (AD). However, most tyrosine kinase inhibitors (TKI) have been thoroughly scrutinized for non-CNS disorders such as cancer, and rheumatoid arthritis. TKI research in neurodegenerative disorders appears to be lagging than in other diseases. Therefore, the present study aims to contribute to this growing area of research by exploring the molecular signaling pathways and examining the efficacy of treatment with lapatinib ditosylate (LAP), as one of the dual TKI targeting EGFR and HER-2 that has not yet been investigated in AD, on cognitive decline induced by ovariectomy with chronic administration of D-galactose (D-gal) in female rats. Ovariectomized adult rats were injected with 150 mg/kg/day D-gal i.p. for 8 weeks to induce AD. Then, they orally administered 100 mg/kg/day LAP for 3 weeks. LAP improved memory as affirmed using Morris water maze and novel object recognition tests. Also, LAP ameliorated histopathological alterations. LAP decreased the expression of p-EGFR, HER-2, glial acidic fibrillary protein (GFAP), p-tau, and beta-amyloid 1-42 (AÝ1-42). Furthermore, it decreased estrogen-related receptors alpha (ERR-Ü), mitochondrial pyruvate carrier-1 (MPC-1), tumor necrosis factor-alpha (TNF-Ü), glutamate receptor-II (GluR-II), NADPH oxidase-1 (NOX-1), mammalian target of rapamycin (p-mTOR), and P38 mitogen-activated protein kinases (P38-MAPK). In contrast, it increased nitric oxide (NO), phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-Akt), and glycogen synthase kinase-3Ý (p-GSK-3Ý)