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Fullerene C60 Derivatives Attenuated Microglia-Mediated Prion Peptide Neurotoxicity

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Prion disorders are progressive neurodegenerative diseases characterized by extensive neuronal loss, which is linked to the extracellular accumulation of the scrapie isoform (PrPSC) of the normal cellular prion protein (PrPC). As microglial activation is a central event in pathogenesis of prion disease, the strategies that reduce microglial activation may have therapeutic benefits. In this study, the neuroprotective effects of hydroxylated C60(C60-OH) and amino modified-C60(C60-NH2) were evaluated by using PrP(106-126)-stimulated BV-2 cells as a model of activated microglia. Herein, we showed that microglial activation in response to PrP(106-126) was effectively attenuated by pretreatment with C60-OH as compared with C60-NH2. C60-OH significantly inhibited the excessive production of inflammatory mediators, such as prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factors (TNF)-α, interleukin (IL)-1β, and IL-6, and blocked the expression of cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS) in PrP(106-126)-stimulated BV-2 cells. C60-OH exerted anti-inflammatory potential by up-regulating the expression of antioxidant enzymes via activation of nuclear factor erythroid 2-related factor 2 (Nrf2). The inhibitory effect of C60-OH against PrP(106-126)-induced inflammatory response was abolished by siRNA of Nrf2. In addition, conditioned culture media taken from PrP(106-126)-stimulated microglia cause apoptotic neuronal cell death, which was suppressed by pretreatment with C60-OH. Take together, these results suggest that C60-OH protects neuronal cells against PrP(106-126)-mediated neurotoxicity through activation of Nrf2 pathway, and provides evidence that fullerene derivatives may have therapeutic potential in prion diseases.
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Keywords: FULLERENES DERIVATIVES; MICROGLIAL ACTIVATION; NEUROPROTECTION; NRF2; PRION DISORDERS

Document Type: Research Article

Publication date: September 1, 2016

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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