5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Citrus Flavonoid Hesperetin Encounters Diabetes-Mediated Alzheimer-Type Neuropathologic Changes through Relieving Advanced Glycation End-Products Inducing Endoplasmic Reticulum Stress

      , , ,
      Nutrients
      MDPI AG

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The present study investigates whether hesperetin, a citrus flavonoid, can encounter advanced glycation end-product (AGE)-induced Alzheimer’s disease-like pathophysiological changes with the underlying mechanisms. SH-SY5Y cells pretreated with hesperetin before stimulation with AGEs (200 μg/mL) were assessed in the following experiments. Hesperetin (40 μmol/L) elevated the reduced cell viability induced by AGEs. Hesperetin ameliorated reactive oxygen species overproduction and the downregulation of superoxide dismutase, glutathione peroxidase, and catalase, triggered by AGEs. Amyloid precursor protein upregulation, accompanied by the increased production of Aβ, caused by AGEs, was reversed by hesperetin. However, hesperetin lowered β-site APP-cleaving enzyme 1 expression, inducing insulin-degrading and neprilysin expression. In addition, hesperetin downregulated the expressions of the AGEs-induced endoplasmic reticulum (ER) stress proteins, including 78-kDa glucose-regulated protein and C/EBP homologous protein, and lowered the phosphorylation of protein kinase R-like ER kinase and activating transcription factor 4. Hesperetin-pretreated cells had a minor apoptotic DNA fragmentation. Hesperetin is able to upregulate Bcl-2 protein expression, downregulate Bax expression, and decrease caspase-12/-9/-3 activity as well, indicating that it inhibits ER stress-mediated neuronal apoptosis. There is a similar effect between hesperetin and positive rosiglitazone control against Aβ aggravation of SH-SY5Y cell injury induced by AGEs. Thus, hesperetin might be a potential agent for treating glycation-induced Aβ neurotoxicity.

          Related collections

          Most cited references44

          • Record: found
          • Abstract: not found
          • Book Chapter: not found

          [13] Catalase in vitro

          Hugo Aebi (1984)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            The amyloid hypothesis of Alzheimer's disease at 25 years

            Abstract Despite continuing debate about the amyloid β‐protein (or Aβ hypothesis, new lines of evidence from laboratories and clinics worldwide support the concept that an imbalance between production and clearance of Aβ42 and related Aβ peptides is a very early, often initiating factor in Alzheimer's disease (AD). Confirmation that presenilin is the catalytic site of γ‐secretase has provided a linchpin: all dominant mutations causing early‐onset AD occur either in the substrate (amyloid precursor protein, APP) or the protease (presenilin) of the reaction that generates Aβ. Duplication of the wild‐type APP gene in Down's syndrome leads to Aβ deposits in the teens, followed by microgliosis, astrocytosis, and neurofibrillary tangles typical of AD. Apolipoprotein E4, which predisposes to AD in > 40% of cases, has been found to impair Aβ clearance from the brain. Soluble oligomers of Aβ42 isolated from AD patients' brains can decrease synapse number, inhibit long‐term potentiation, and enhance long‐term synaptic depression in rodent hippocampus, and injecting them into healthy rats impairs memory. The human oligomers also induce hyperphosphorylation of tau at AD‐relevant epitopes and cause neuritic dystrophy in cultured neurons. Crossing human APP with human tau transgenic mice enhances tau‐positive neurotoxicity. In humans, new studies show that low cerebrospinal fluid (CSF) Aβ42 and amyloid‐PET positivity precede other AD manifestations by many years. Most importantly, recent trials of three different Aβ antibodies (solanezumab, crenezumab, and aducanumab) have suggested a slowing of cognitive decline in post hoc analyses of mild AD subjects. Although many factors contribute to AD pathogenesis, Aβ dyshomeostasis has emerged as the most extensively validated and compelling therapeutic target.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              The neuropathological diagnosis of Alzheimer’s disease

              Alzheimer’s disease is a progressive neurodegenerative disease most often associated with memory deficits and cognitive decline, although less common clinical presentations are increasingly recognized. The cardinal pathological features of the disease have been known for more than one hundred years, and today the presence of these amyloid plaques and neurofibrillary tangles are still required for a pathological diagnosis. Alzheimer’s disease is the most common cause of dementia globally. There remain no effective treatment options for the great majority of patients, and the primary causes of the disease are unknown except in a small number of familial cases driven by genetic mutations. Confounding efforts to develop effective diagnostic tools and disease-modifying therapies is the realization that Alzheimer’s disease is a mixed proteinopathy (amyloid and tau) frequently associated with other age-related processes such as cerebrovascular disease and Lewy body disease. Defining the relationships between and interdependence of various co-pathologies remains an active area of investigation. This review outlines etiologically-linked pathologic features of Alzheimer’s disease, as well as those that are inevitable findings of uncertain significance, such as granulovacuolar degeneration and Hirano bodies. Other disease processes that are frequent, but not inevitable, are also discussed, including pathologic processes that can clinically mimic Alzheimer’s disease. These include cerebrovascular disease, Lewy body disease, TDP-43 proteinopathies and argyrophilic grain disease. The purpose of this review is to provide an overview of Alzheimer’s disease pathology, its defining pathologic substrates and the related pathologies that can affect diagnosis and treatment. Electronic supplementary material The online version of this article (10.1186/s13024-019-0333-5) contains supplementary material, which is available to authorized users.
                Bookmark

                Author and article information

                Journal
                NUTRHU
                Nutrients
                Nutrients
                MDPI AG
                2072-6643
                February 2022
                February 10 2022
                : 14
                : 4
                : 745
                Article
                10.3390/nu14040745
                35215394
                86c7c5ab-918a-44e6-bbf0-356853d7b9c8
                © 2022

                https://creativecommons.org/licenses/by/4.0/

                History

                Comments

                Comment on this article