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Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration
We report that a high-fat/high-cholesterol diet leads to an i ncrease in S100A8 production in the brain. In CYP27Tg, we report an increase of S100A8 and its receptor RAGE in the hippocampus under elevated 27-OH in the brain. Using siRNA, we found that 27-OH upregulation of RAGE in astrocytes and neurons is mediated by the nuclear receptor RXRγ. Silencing RXRγ in neurons prevented 27-OH-mediated upregulation of RAGE. These results show that S100A8 alarmin and RAGE respond to high levels of 27-OH in the brain in both neurons and astrocytes through RXRγ. Our study supports the notion that 27-OH mediates detrimental effects...
Source: Molecular Neurobiology - August 27, 2021 Category: Neurology Source Type: research

Naringenin Upregulates AMPK-Mediated Autophagy to Rescue Neuronal Cells From β-Amyloid (1–42) Evoked Neurotoxicity
AbstractDeposition of an amyloid- β peptide is one of the first events in the pathophysiology of Alzheimer’s disease (AD) and is clinically characterized by Aβ plaques, tau tangles, and behavioral impairments that lead to neuronal death. A substantial number of studies encourage targeting the skewness in the production and degra dation of amyloid-β could be among the promising therapies in the disease. Neuronal autophagy has emerged for an essential role in the degradation of such toxic aggregate-prone proteins in various neurodegenerative diseases. We profiled a small library of common dietary compounds and identifie...
Source: Molecular Neurobiology - June 15, 2020 Category: Neurology Source Type: research

Activation of Nrf2 Pathway Contributes to Neuroprotection by the Dietary Flavonoid Tiliroside
This study was aimed at investigating the molecular mechanisms involved in the inhibition of neuroinflammation and neurotoxicity by tiliroside. The effects of tiliroside on Nrf2 and SIRT1 activities in BV2 microglia and HT22 hippocampal neurons were investigated using immunoblotting and DNA binding assays. The roles of Nrf2 and SIRT1 in the anti-inflammatory activity of tiliroside were further investigated using RNA interference experiments. HT22 neuronal viability was determined by XTT, calcium influx, DNA fragmentation assays. The effect of tiliroside on MAP2 protein expression in HT22 neurons was investigated using west...
Source: Molecular Neurobiology - March 5, 2018 Category: Neurology Source Type: research

A Hypothalamic Leptin-Glutamate Interaction in the Regulation of Sympathetic Nerve Activity.
In conclusion, these studies provide evidence that within the hypothalamic nuclei, leptin-glutamate signaling regulates the sympathetic activation. This may contribute to the sympathoexcitation commonly observed in obesity-related T2D. PMID: 28845307 [PubMed - in process]
Source: Neural Plasticity - August 30, 2017 Category: Neurology Authors: Zheng H, Liu X, Li Y, Patel KP Tags: Neural Plast Source Type: research