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• W2799988161 abstract "Neuroinflammation causes neurotoxic injury and underlies the pathogenesis of neurodegenerative disorders including Alzheimer's disease (AD). Astrocytes are the predominant immunoregulatory cells in AD. Oleanolic acid (OA) is a promising anti-inflammatory therapeutic agent that can ameliorate cerebral damage in ischemic environments, but its role in AD remains poorly elucidated. Here, preconditioning with OA inhibited the transcription and secretion of inflammatory cytokines IL-6, TNF-α, and IL-1β in amyloid-beta peptide (Aβ)-activated astrocytes. Moreover, OA ameliorated primary neuron death triggered by incubation in conditioned medium from Aβ-treated astrocytes. Furthermore, OA also suppressed Aβ-induced expression and production of group IIA secretory phospholipase A2 (sPLA2-IIA) in astrocytes. Supernatants supplemented with exogenous sPLA2-IIA reversed the protective role of OA against astrocyte activation-mediated neurotoxicity by suppressing cell viability and increasing LDH release, apoptosis, the contents of neurotoxic mediator arachidonic acid, and prostaglandin D2. Simultaneously, treatment with sPLA2 inhibitor aristolochic acid also counteracted neurotoxicity induced by Aβ-activated astrocytes through increasing cell viability, inhibiting cell apoptosis, and reducing the releases of arachidonic acid and prostaglandin D2. Additionally, OA restrained Ca2+ influx in neurons after incubation with supernatants from Aβ-activated astrocytes, which was abrogated by adding sPLA2-IIA. Activating Ca2+ signaling with BayK, an L-type Ca2 + channel agonist, reversed the beneficial role of OA against neurotoxicity induced by astrocyte activation-mediated inflammatory response. OA also ameliorated cognitive deficits in an adolescent rat model of Aβ-evoked AD. These findings confirm that OA abrogates neuroinflammation and subsequent neurotoxicity induced by conditioned media from Aβ-activated astrocytes in sPLA2-IIA mediated-calcium signals. Therefore, OA may protect neurons from injury caused by neighboring astrocyte activation in AD, indicating a promising therapeutic strategy against AD." @default.
• W2799988161 created "2018-05-17" @default.
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• W2799988161 date "2018-07-01" @default.
• W2799988161 modified "2023-10-16" @default.
• W2799988161 title "Oleanolic acid protects against cognitive decline and neuroinflammation-mediated neurotoxicity by blocking secretory phospholipase A2 IIA-activated calcium signals" @default.
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• W2799988161 doi "https://doi.org/10.1016/j.molimm.2018.04.015" @default.
• W2799988161 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29747052" @default.
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