Fas/CD95 ligation induces proliferation of primary fetal astrocytes through a mechanism involving caspase 8-mediated ERK activation.

Background: Fas/CD95 is the best-studied member of the death receptor (DR) superfamily in the central nervous system where it can trigger cellular responses other than apoptosis, including the promotion of neurogenesis and neuritogenesis, stimulation of the progression of gliomas, and regulation of the immune response of astrocytes.

Methods: We have investigated the role of Fas/CD95 in the regulation of the proliferation of fetal astrocytes in vitro, as well as the signalling pathways involved.

Results: Fas/CD95 ligation stimulated the proliferation of primary fetal astrocytes, through a mechanism that depends on the activation of caspase 8 and subsequent phosphorylation of extracellular signal regulated kinase (ERK).

Bimodal effect of interferon-β on astrocyte proliferation and survival: Importance of nuclear factor-κB.

Accumulating evidence indicates that interferon-β (IFN-β) can modify the complex immunopathogenic scenario causing clinical relapse activity and disease progression in MS. However, the beneficial effects of IFN-β in MS patients may also depend on non-immune mechanisms, including the modulation of astrocyte function. In the present report, we have shown that, depending on the dose, IFN-β treatment can either promote astrocyte proliferation and survival, or result astrocyte death.

Resistance of neonatal primary astrocytes against Fas-induced apoptosis depends on silencing of caspase 8.

In the present report, we have found that primary fetal astrocytes express caspase 8 and undergo apoptosis in response to Fas ligation. In contrast, neonatal astrocytes do not express detectable levels of the enzyme and are resistant to Fas killing. Fas-induced apoptosis can be restored in these cells by up-regulation of caspase 8 expression by means of transient transfection with a caspase 8-encoding plasmid.

Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series.

Niemann-Pick disease type C (NP-C) is an inherited neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Different clinical forms have been defined based on patient age at onset: perinatal, early-infantile (EI), late-infantile (Li), juvenile and adult. We evaluated the efficacy and tolerability of miglustat in 16 symptomatic NP-C patients, with comparative reference to one neurologically asymptomatic, untreated patient.

Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain.

Objective: Toxic thyroid adenoma (TA) is a common cause of hyperthyroidism. Mutations in the TSH receptor (TSHR) gene, and less frequently in the adenylate cyclase-stimulating G alpha protein (GNAS) gene, are well established causes of TA in Europe. However, genetic causes of TA remain unknown in a small percentage of cases.