Biology subjects

EL Fatimy, R.

Publications and source records attributed to EL Fatimy, R..

2 recordsLinked to original sources

bioRxiv2020

NAD+ prevents septic shock by non-canonical inflammasome blockade and IL-10

Septic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral infections. Non-canonical inflammasome activation is crucial in the development of septic shock promoting pyroptosis and pro-inflammatory cytokine production via caspase-11 and Gasdermin-D (GSDMD). Here, we show that NAD+ treatment protected mice towards bacterial and LPS induced endotoxic shock by blocking the non-canonical inflammasome specifically. NAD+ administration impeded systemic IL-1{beta} and IL-18 production and GSDMD-mediated pyroptosis of macrophages via the IFN-{beta}/STAT-1 signaling machinery. More importantly, NAD+ administration not only improved casp-11 KO (knockout) survival but rendered WT mice completely resistant to septic shock via the IL-10 signaling pathway that was independent from the non-canonical inflammasome. Here, we delineated a two-sided effect of NAD+ blocking septic shock through a specific inhibition of the non-canonical inflammasome and promoting immune homeostasis via IL-10, underscoring its unique therapeutic potential.

immunology↗

bioRxiv2018

MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways

MicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here we describe a neuroprotective function of miR-132, the miRNA most significantly down-regulated in Alzheimers disease. miR-132 protects mouse and human wild-type neurons and more vulnerable Tau-mutant primary neurons against amyloid {beta}-peptide (A{beta}) and glutamate excitotoxicity. It lowers the levels of total, phosphorylated, acetylated, and cleaved forms of Tau implicated in tauopathies, promotes neurite elongation and branching, and reduces neuronal death. Similarly, miR-132 attenuates PHF Tau pathology and neurodegeneration and enhances long-term potentiation in the P301S Tau transgenic mice. The neuroprotective effects are mediated by direct regulation of the Tau modifiers acetyltransferase EP300, kinase GSK3{beta}, RNA-binding protein Rbfox1, and proteases Calpain 2 and Caspases 3/7. These data suggest miR-132 as a master regulator of neuronal health and indicate that miR-132 supplementation could be of therapeutic benefit for the treatment of Tau-associated neurodegenerative disorders.

neuroscience↗