Krabbe Disease


Findings from University of Siena provide new insights into apoptosis cell biology



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2007 OCT 2 -- Fresh data on apoptosis are presented in the report "Psychosine-induced apoptosis and cytokine activation in immune peripheral cells of Krabbe patients." According to recent research from Siena, Italy, "Globoid cell leukodystrophy or Krabbe disease (KD), is a hereditary disorder caused by galactosylceramidase deficiency. Progressive accumulation of psychosine is considered to be the critical pathogenetic mechanism of cell death in the Krabbe brain."

"Psychosine mechanism of action has not been fully elucidated. It seems to induce apoptosis in oligodendrocytes through a mitochondrial pathway and to up-regulate inflammatory cytokines production resulting in oligodendrocyte loss. Our aim was to evaluate the role of psychosine in apoptotic cell death and inflammatory response in a group of patients affected by KD using peripheral blood lymphocytes (PBLs) and peripheral blood mononuclear cells (PBMCs) as a cellular model. PBLs from KP and healthy controls were exposed to 20 microM psychosine and analysed by flow cytometry, agarose gel electrophoresis and fluorescence microscopy. Our results showed that psychosine induces apoptosis in PBLs through a mitochondrial pathway, but the apoptotic response was quite low especially KP. The role of psychosine in the up-regulation of cytokines (TNF-alpha, IL8 and MCP1) has been evaluated by ELISA in PBMCs from KP and controls after stimulation with LPS and phytohemagglutinin. Both in basal condition and after LPS stimulation, cells from KP showed a significant increase in TNF-alpha production, reduced MCP1 levels and no modification in IL8. These results indicate that lymphomonocytes from KP had a basal proinflammatory pattern that was amplified by psychosine," wrote P. Formichi and colleagues, University of Siena.

The researchers concluded: "The reduced apoptotic response and the atypical cytokine production observed in our experiments, suggest an involvement of inflammatory pattern in immune peripheral cells of KP."

Formichi and colleagues published their study in the Journal of Cellular Physiology (Psychosine-induced apoptosis and cytokine activation in immune peripheral cells of Krabbe patients. Journal of Cellular Physiology, 2007;212(3):737-43).

For additional information, contact P. Formichi, University of Siena, Dept. of Neurological and Behavioural Sciences, Siena, Italy.

Publisher contact information for the Journal of Cellular Physiology is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Keywords: Italy, Siena, Apoptosis Cell Biology, Apoptosis, Cell Biology, Cellular Physiology.

This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.