Ergosterol promotes neurite outgrowth, inhibits amyloid-beta synthesis, and extends longevity: In vitro neuroblastoma and in vivo Caenorhabditis elegans evidence

Aims: Alzheimer's disease (AD), the most common neurodegenerative disorder associated with aging, is characterized by amyloid-beta (A beta) plaques in the hippocampus. Ergosterol, a mushroom sterol, exhibits neuroprotective activities; however, the underlying mechanisms of ergosterol in promoting neurite outgrowth and preventing A beta associated aging have never been investigated. We aim to determine the beneficial activities of ergosterol in neuronal cells and Caenorhabditis elegans (C. elegans). Materials and methods: The neuritogenesis and molecular mechanisms of ergosterol were investigated in wildtype and A beta precursor protein (APP)-overexpressing Neuro2a cells. The anti-amyloidosis properties of ergosterol were determined by evaluating in vitro A beta production and the potential inhibition of A beta-producing enzymes. Additionally, AD-associated transgenic C. elegans was utilized to investigate the in vivo attenuating effects of ergosterol. Key findings: Ergosterol promoted neurite outgrowth in Neuro2a cells through the upregulation of the transmembrane protein Teneurin-4 (Ten-4) mRNA and protein expressions, phosphorylation of the extracellular signal-regulated kinases (ERKs), activity of cAMP response element (CRE), and growth-associated protein-43 (GAP-43). Furthermore, ergosterol enhanced neurite outgrowth in transgenic Neuro2A cells overexpressing either the wild-type APP (Neuro2a-APPwt) or the Swedish mutant APP (Neuro2a-APPswe) through the Ten-4/ ERK/CREB/GAP-43 signaling pathway. Interestingly, ergosterol inhibited A beta synthesis in Neuro2a-APPwt cells. In silico analysis indicated that ergosterol can interact with the catalytic sites of beta- and gamma-secretases. In A beta-overexpressing C. elegans, ergosterol decreased A beta accumulation, increased chemotaxis behavior, and prolonged lifespan. Significance: Ergosterol is a potential candidate compound that might benefit AD patients by promoting neurite outgrowth, inhibiting A beta synthesis, and enhancing longevity

Ergosterol isolated from cloud ear mushroom (Auricularia polytricha) attenuates bisphenol A-induced BV2 microglial cell inflammation

© 2022 Elsevier LtdBisphenol A (BPA) has been reported to have neurotoxic properties that may increase the risk of neurodegenerative diseases by inducing neuroinflammation. Auricularia polytricha (AP) is an edible mushroom with several medicinal properties. Herein, the anti-neuroinflammatory effects of AP extracts against BPA-induced inflammation of BV2 microglial cells were investigated. Hexane (APH) and ethanol (APE) extracts of AP inhibited BPA-induced neuroinflammation in BV2 microglia by reducing microglial activation and the expression of pro-inflammatory cytokines. These anti-inflammatory effects were regulated by the NF-κB signaling pathway. In addition, APH and APE exhibited antioxidative effects by increasing the activity of the SOD-1 enzyme and restoring the accumulation of reactive oxygen species (ROS) in BPA-induced BV2 cells. Moreover, the conditioned medium prepared using BPA-induced BV2 cells demonstrated that the presence of APH or APE could attenuate ROS production in HT-22 cells. Further, ergosterol was isolated from APE and also showed anti-inflammatory and antioxidative activities. In conclusion, AP extracts and ergosterol attenuated neuroinflammation against BPA induction in BV2 microglial cells through the NF-κB signaling pathway.N