RESUMEN
Lipid rafts provide a platform for regulating cellular functions and participate in the pathogenesis of several diseases. However, the role of caveolin-1 in this process has not been elucidated definitely in neuron. Thus, this study was performed to examine whether caveolin-1 can regulate amyloid precursor protein (APP) processing in neuronal cells and to identify the molecular mechanisms involved in this regulation. Caveolin-1 is up-regulated in all parts of old rat brain, namely hippocampus, cerebral cortex and in elderly human cerebral cortex. Moreover, detergent-insoluble glycolipid (DIG) fractions indicated that caveolin-1 was co-localized with APP in caveolae-like structures. In DIG fractions, bAPP secretion was up-regulated by caveolin-1 over-expression, which was modulated via protein kinase C (PKC) in neuroblastoma cells. From these results we conclude that caveolin-1 is selectively expressed in senescent neurons and that it induces the processing of APP by beta-secretase via PKC downregulation.
Asunto(s)
Ratas , Persona de Mediana Edad , Humanos , Animales , Anciano de 80 o más Años , Anciano , Regulación hacia Arriba , Receptores de Superficie Celular/metabolismo , Proteína Quinasa C/metabolismo , Microscopía Electrónica , Caveolina 1/metabolismo , Caveolas/metabolismo , Encéfalo/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/metabolismo , Envejecimiento/metabolismoRESUMEN
BACKGROUND: Estrogen is beneficial to patients with Alzheimer's disease but has a limited clinical use due to its proliferative and oncogenic effects on non-neuronal estrogen responsive cells. METHODS: In an attempt to find an estrogen substitute that retains the beneficial effects of estrogen with minimal side effects, we compared the neuroprotective and proliferative effects of genistein, a selective estrogen receptor betaagonist, with those of estrogen. RESULTS: Genistein and 17beta-estradiol showed comparable levels of protection against Abeta-induced death of cultured SH-SY5Y human neuroblastoma cells, which was blocked by an estrogen receptor antagonist, ICI 182, 780. On the other hand, 17beta-estradiol, but not geninstein, induced proliferation of uterine endometrial cells. CONCLUSIONS: Our results suggest genistein as a potential alternative to estrogen in the treatment of Alzheimer's disease.
Asunto(s)
Humanos , Enfermedad de Alzheimer , Muerte Celular , Estrógenos , Genisteína , Mano , Neuroblastoma , Fármacos NeuroprotectoresRESUMEN
BACKGROUND: Ginseng extracts, known to enhance bodily functions including learning and memory, were reported to have in vitro neuroprotective activity in vitro. Here We demonstrate the possible therapeutic effects of ginsenosides on the cell culture model of Alzheimer's Disease (AD). We tested whether Rb1 or Rg1 , major components of ginseng saphonins, protects neuronal cells from the toxic effect of beta-amyloid (Abeta), which is regarded to be the main neurotoxic substrate in the AD. METHOD: B103 cells, rat brain-derived neuronal cells, were cultured and the extent of neuroprotective effects of ginsenosides on the cytotoxicity induced by exogenous Abeta25-35 was were measured by MTT assay. RESULTS: Treatment of Rb1 and Rg1 at various concentrations (l0nM, 50nM, and 1 micrometer, respectively) in B103 cells did not show any dose-dependent neurotoxic effects. Rg1 (1 micrometer) significantly blocked the neurotoxic effect of Abeta2 5 - 3 5 (50 micrometer)(P<0.05). Rb1 at concentration of 1 micrometer also had some neuroprotective effects, but not as effective as Rg1 . These neuroprotective effects are comparable to the one of estrogen (1.8nM). CONCLUSIONS: This experiment suggests the potential beneficial effects of ginseng in the treatment of AD.