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[D. Medicine/Translational Research] D-12



                  Long-Term Treatment of Cuban Policosanol Attenuates


               Abnormal Oxidative Stress and Inflammatory Response via


                           Amyloid Plaques Reduction in 5xFAD Mice




                                      Jinho Kim¹, Yoo-Hun Suh², Keun-A Chang¹,²,³*

            ¹Department of Health Sciences and Technology, Gachon University, Incheon 21999, Korea, ²Neuroscience

         Research Institute, Gachon University, Incheon 21565, Korea, ³Department of Pharmacology, College of Medicine,

                                          Gachon University, Incheon 21999, Korea




        Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline or dementia, the
        number of patients with AD is continuously increasing. Although a lot of great progress has been made in the

        research  and  development  of  AD  therapeutics,  there  is  no  fundamental  cure  for  this  disease  yet.  This  study
        demonstrated the memory-improving effects of Cuban policosanol (PCO) in 5xFAD mice, which is an animal model

        of AD. Following 4-months of treatment with PCO in 5xFAD mice, we found that the number of amyloid plaques
        decreased  in the brain compared to the  vehicle-treated 5xFAD mice. Long-term PCO treatment in 5xFAD mice

        resulted in the reduction of gliosis and abnormal inflammatory cytokines level (interleukin [IL]-1β, IL-6, and tumor
        necrosis factor [TNF]-α) in the cortex and hippocampus. Levels of lipid peroxide (4-hydroxynonenal [4-HNE]) and
        superoxide dismutase (SOD1 and SOD2) levels were also recovered in the brains of PCO-treated 5xFAD mice. Notably,

        PCO  administration  reduced  memory  deficits  in  the  passive  avoidance  test,  as  well  as  synaptic  loss  (PSD-95,

        synaptophysin) in 5xFAD mice. Collectively, we identified the potential effects of PCO as a useful supplement to
        delay or prevent AD progression by inhibiting the formation of Aβ plaques in the brain.
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