iNSC suppress macrophage-induced inflammation by repressing COX-2. In Vitro Cell Dev Biol Anim. 2015 Feb;51(2):157-64 Authors: Kim JH, Sun W, Han DW, Moon HJ, Lee J Abstract PMID: 25248435 [PubMed - indexed for MEDLINE] Physiological and pathological roles of the γ-secretase complex. Brain Res Bull. 2016 Apr 28; Authors: Carroll CM, Li YM Abstract PMID: 27133790 [PubMed - as supplied by publisher]
pubmed: alzheimer's and stem...
NCBI: db=pubmed; Term=alzheimer's and stem cell therapy
Brain inflammation causes cell damage and death in diseases such as Alzheimer's and Parkinson's. In this study, we investigated whether early induced neural stem cells (iNSCs) could protect against cell death after treatment with THP1-derived macrophages. We developed an inflammatory model system with THP1-derived macrophages and cortical neuronal cells and investigated the therapeutic efficacy of iNSC against macrophage-induced inflammation in this model. Apoptosis was confirmed by double immunocytochemistry with NeuN and 4',6-diamidino-2-phenylindole using terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling. Cortical neuronal cells cultured with iNSCs exhibited fewer apoptotic cells than did cultures without iNSCs. The levels of inflammatory cytokines and vascular endothelial growth factor (VEGF) were analyzed by enzyme-linked immunosorbent assay. Cells cultured with iNSCs had lower levels of inflammatory cytokines and higher VEGF levels than those cultured without iNSCs. Western blot analysis for cyclooxygenase-2 (COX-2) showed a significantly lower level of COX-2 in cells cultured with iNSCs than in those cultured without iNSCs. Thus, early iNSCs administration reduced inflammation associated with neurological recovery, and this effect is mediated by COX-2 regulation. Our results suggest that iNSCs have potential therapeutic relevance, because they display strong anti-inflammatory functions that promote neuroprotection thorough the inflammatory response.
pubmed: alzheimer's and stem...
NCBI: db=pubmed; Term=alzheimer's and stem cell treatment
Gamma-secretase (GS) is an enzyme complex that cleaves numerous substrates, and it is best known for cleaving amyloid precursor protein (APP) to form amyloid-beta (Aβ) peptides. Aberrant cleavage of APP can lead to Alzheimer's disease, so much research has been done to better understand GS structure and function in hopes of developing therapeutics for Alzheimer's. Therefore, most of the attention in this field has been focused on developing modulators that reduce pathogenic forms of Aβ while leaving Notch and other GS substrates intact, but GS provides multiple avenues of modulation that could improve AD pathology. GS has complex regulation, through its essential subunits and other associated proteins, providing other targets for AD drugs. Therapeutics can also alter GS trafficking and thereby improve cognition, or move beyond Aβ entirely, effecting Notch and neural stem cells. GS also cleaves substrates that effect synaptic morphology and function, presenting another window by which GS modulation could improve AD pathology. Taken together, GS presents a unique cross road for neural processes and an ideal target for AD therapeutics.
iNSC suppress macrophage-induced inflammation by repressing COX-2.
In Vitro Cell Dev Biol Anim. 2015 Feb;51(2):157-64
Authors: Kim JH, Sun W, Han DW, Moon HJ, Lee J
PMID: 25248435 [PubMed - indexed for MEDLINE]
Physiological and pathological roles of the γ-secretase complex.
Brain Res Bull. 2016 Apr 28;
Authors: Carroll CM, Li YM
PMID: 27133790 [PubMed - as supplied by publisher]