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Ciliary neurotrophic factor (CNTF) has recently generated great interest due to its potential as a therapeutic agent for the treatment of human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Because the systemic half-life of CNTF is only in the order of a few minutes, continuous delivery of this trophic factor could be attractive or(More)
Bcl-2 and its analogs protect different classes of neurons from apoptosis in several experimental situations. These proteins may therefore provide a means for treatment of neurodegenerative diseases. We examined the effects of Bcl-2 overexpression in a genetic mouse model with motor neuron disease (progressive motor neuronopathy/pmn). Pmn/pmn mice lose(More)
Glial cell line-derived neurotrophic factor (GDNF), a member of the TG F-beta superfamily, has been shown to be a highly potent neurotrophic factor that enhances survival of various neuronal cell types including motoneurons. To assess its therapeutic potential in treating neurodegenerative diseases such as amyotrophic lateral sclerosis, we treated mutant(More)
Glial cell line-derived neurotrophic factor (GDNF) has been postulated to be a specific dopaminergic neurotrophic factor since it selectively enhances the survival of dopaminergic neurones in vitro. We report here that GDNF can also act as a neurotrophic factor for motoneurones. GDNF released by GDNF-transfected BHK cells increases the activity of choline(More)
The well-characterized human teratocarcinoma line Ntera2 (NT2) can be differentiated into mature neurons. We have significantly shortened the time-consuming process for generating postmitotic neurons to approximately 4 weeks by introducing a differentiation protocol for free-floating cell aggregates and a subsequent purification step. Here, we characterize(More)
We describe a novel cell culture protocol for the generation of neurons from a human teratocarcinoma cell line. These neurons were used to investigate hypoxic-ischaemic cell damage and for developing neuroprotective strategies. Cultures of human model neurons should eventually serve to reduce the number of experimental animals in cerebral stroke research.
Cells from the human teratocarcinoma line NTera-2 can be induced to terminally differentiate into postmitotic neurons when treated with retinoic acid. However, this differentiation process is rather time consuming as it takes between 42 and 54 days. Here, we propose a modified differentiation protocol which reduces the time needed for differentiation(More)
The neurodegenerative disease amyotrophic lateral sclerosis (ALS) results from the progressive loss of motoneurons, leading to death in a few years. Ciliary neurotrophic factor (CNTF), which decreases naturally occurring and axotomy-induced cell death, may result in slowing of motoneuron loss and has been evaluated as a treatment for ALS. Effective(More)
Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3Rs” (reduction, replacement, and refinement) of animal testing, alternative testing strategies are needed in order to refine and(More)
Neurotrophic factors hold promise for the treatment of neurodegenerative diseases. Intrathecal transplantation of polymer encapsulated cell lines genetically engineered to release neurotrophic factors provides a means to deliver them continuously behind the blood-brain barrier. Long-term delivery, however, may benefit from the use of conditionally mitotic(More)