1,721,066 research outputs found
Editorial [Hot Topic Stem Cells as a Tool for Biomedical Applications Guest Editor: Martino Sabata]
No full textApprocci di terapia genica per le malattie da accumulo metabolico lisosomiale con coinvolgimento neurologico
No full textRelazione su invit
Le cellule staminali per la terapia delle GM2 gangliosidosi
No full textCellule staminali somatiche. Relazione su invit
STEM CELLS AND GM2 GANGLIOSIDOSIS. Updating on diagnosis and therapies of lysosomal diseases.
No full textRevie
RNA interference as a tool for Alzheimer's disease therapy
No full textRNA interference is a biological process that controls gene silencing in all living cells. Targeting the RNA interference system represents a novel therapeutic strategy able to intercede with multiple disease-related genes and to target many neurodegenerative diseases. Recently, the design of small interfering RNA-selective compounds has become more straightforward because of the significant progress made in predictive modeling for new therapeutic approaches. Although in vivo delivery of RNA interference remains a significant obstacle, new data show that RNAi blocks gene function in vivo, suggesting a potential therapeutic approach for humans. Some groups have demonstrated the efficacy of RNAi therapy in Alzheimer's disease. Results, based on animal models, show a down-regulation of the amyloid precursor protein and a consequent reduction of the amyloid-beta peptide accumulation in the brain or the inactivation of beta-secretase (BACE1). Indeed, lentiviral vectors expressing siRNAs targeting BACE1 reduce amyloid production and the neurodegenerative and behavioural deficit in APP transgenic mice. This review highlights recent advances in RNA research and focuses on strengths and weaknesses of RNAi compounds in Alzheimer's disease
Acid glycohydrolases activities in linphomonocytes plasma-membrane of patients with multiple sclerosis
No full textInfluence of cell differentiation and protein kinase C activation on sub-cellular distribution of beta-N-acetylhexosaminidases of HL 60 cells.
No full textThere have been several accounts regarding the alterations of the lysosomal enzyme beta-N-acetylhexosaminidase in human leukaemic cells. In addition to Hex A (alpha beta) and Hex B (beta beta) forms, leukaemic cells contain a third isoenzyme displaying many characteristics in common with Hex S, the alpha alpha dimer representing the residual activity in patients with Sandhoff's disease. In the human leukaemic cell line HL 60, A (alpha beta) and S (alpha alpha) are the most abundant forms. Sub-cellular fractionation of HL 60 cells showed that both A and S forms were present in the lysosomal and post-lysosomal fractions, however, a proportion of activity was found to be associated with the plasma membrane. The phorbol ester 12-O-tetra-decanoylphorbol-13-acetate (TPA) exerts complex effects on the physiology of HL 60 cells, leading to cell differentiation along the macrophage pathway and including activation of Protein Kinase C (PKC). In order to assess the extent to which cell differentiation and PKC activation plays a role in modulating the expression of hexosaminidase during cell differentiation, we treated HL 60 cells with TPA and in parallel with the more specific activator of PKC, 1-oleoyl-2-acetyl diglycerol (OAG) which does not cause cell differentiation. We observed that 24 h exposure of HL 60 cells to TPA or OAG produced significant modification of the hexosaminidase isoenzyme pattern of HL 60 cells. The most remarkable effect was seen in both cases in the plasma membrane fraction. Taken together, our results suggest a correlation between hexosaminidase expression and kinase(s) activation
Proteomics and Epigenetic Mechanisms in Stem Cells
No full textEpigenetic mechanisms orchestrate inheritable concerted networks essential for chromatin remodeling. Molecular
interplays include post-translational modifications to histones, DNA methylation, activity of small non coding RNAs,
govern activation and silencing of gene expression and define the molecular basis of pluripotency, reprogramming, early
human development and differentiation.
The implications of epigenetic regulation in maintaining stem cell fate determination are well known. Thus: (i) embryonic
stem cells (ESCs) seem to employ selected histone modification mechanisms for maintaining pluripotency and for the activation
of multipotency programs; (ii) induced pluripotent stem cells, while recapitulating the overall features of the
ESCs epigenome, express differences in DNA methylation; (iii) the lineage-restricted process of adult mesenchymal stem
cell differentiation involves epigenetic regulation and consists of a unique pattern of DNA methylation and histone modifications;
(iv) the epigenetic profiles of adult stem cells correlate with a more restricted differentiation potential as compared
to ESCs.
This review will discuss the role of epigenetic regulation in pluripotency, stemness and cell fate specification, taking advantage
of recent discoveries showing that mass spectrometry and proteomics are become indispensable tools in epigenetic
research
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