Alzheimer's disease (AD) is a neurodegenerative disease characterised by the presence of β-amyloid plaques and acetylcholine depletion leading to neurobehavioral defects. AD was contributed also with downregulation of TGF-β1/SMAD2 and GSK3β/β-catenin pathways. Simvastatin (SMV) improved memory function experimentally and clinically. Hence, this study aimed to investigate the mechanistic role of SMV against aluminium chloride (AlCl) induced neurobehavioral impairments. AD was induced by AlCl (50 mg/kg) for 6 weeks. Mice received Simvastatin (10 or 20 mg/kg) or Donepezil (3 mg/kg) for 6 weeks after that the histopathological, immunohistochemical and biochemical test were examined. Treatment with SMV improved the memory deterioration induced by AlCl with significant recovery of the histopathological changes This was concomitant with the decrease of AChE and Aβ . SMV provides its neuroprotective effect through upregulating the protein expression of β-catenin, TGF-β1 and downregulating the expression of GSK3β, TLR4 and p-SMAD2.
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| http://dx.doi.org/10.1016/j.etap.2023.104220 | DOI Listing |
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