Jonathan W Francis

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Glial cell line-derived neurotrophic factor (GDNF) has shown robust neuroprotective and neuroreparative activities in various animal models of Parkinson's Disease or amyotrophic lateral sclerosis (ALS). The successful use of GDNF as a therapeutic in humans, however, appears to have been hindered by its poor bioavailability to target neurons in the central(More)
Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by mutations in the survival motor neuron gene (SMN1). While it has been shown that the SMN protein is involved in spliceosome biogenesis and pre-mRNA splicing, there is increasing evidence indicating that SMN may also perform important functions in the nucleolus. We demonstrate here(More)
The mechanism and cofactor requirements of exocytotic membrane fusion in neutrophils are unknown. Cytosolic proteins have been implicated in membrane fusion events. We assessed neutrophil cytosol for the presence of fusogenic proteins using a liposome fusion assay (lipid mixing). A fusogenic 36-kD protein containing amino acid sequence homology with human(More)
Increased levels of CuZn superoxide dismutase (SOD-1) are cytoprotective in experimental models of neurological disorders associated with free radical toxicity (e.g. stroke, trauma). Targeted delivery of SOD-1 to central nervous system neurons may therefore be therapeutic in such diseases. The nontoxic C-fragment of tetanus toxin (TTC) possesses the nerve(More)
The cholinergic agonists oxotremorine, oxotremorine-1, oxotremorine-3, arecoline and BM 123 (N-[4-(2-chloroethylmethylamino)-2-butynyl]-2-pyrrolidone) were used to investigate the role of muscarinic receptors in the regulation of acetylcholine (Ach) concentration in the whole mouse brain. Intravenous oxotremorine, oxotremorine-1, oxotremorine-3 and(More)
This study describes the expression, purification, and characterization of a recombinant fusion toxin, DAB(389)TTC, composed of the catalytic and membrane translocation domains of diphtheria toxin (DAB(389)) linked to the receptor binding fragment of tetanus toxin (C-fragment). As determined by its ability to inhibit cellular protein synthesis in primary(More)
Spinal muscular atrophy (SMA) is a degenerative disorder of spinal motor neurons caused by homozygous mutations in the survival motor neuron (SMN1) gene. Because increased tissue levels of human SMN protein (hSMN) in transgenic mice reduce the motor neuron loss caused by murine SMN knockout, we engineered a recombinant SMN fusion protein to deliver(More)
Binding affinities of adinazolam and its metabolite mono-N-demethyladinazolam, U-42352, to the brain tissue are not altered by the presence of proadifen (SKF-525A) in [3H]flunitrazepam [( 3H]FNZ) binding assays in-vitro. Pretreatment of mice with proadifen significantly blocked the ability of intravenously administered adinazolam to inhibit [3H]FNZ binding(More)
Entry of most compounds into the CNS is impeded by the blood-brain barrier (BBB). Because vascular endothelial growth factor (VEGF) is important in the formation and maintenance of the BBB and is known to modulate BBB permeability in newborn rodents, we tested the hypothesis that VEGF may enhance BBB permeability in adult mice. We examined the effect of(More)
Spinal muscular atrophy is caused by defects in the survival motor neuron (SMN) gene. To better understand the patterns of expression of SMN in neuronal cells and tissues, we raised a polyclonal antibody (abSMN) against a synthetic oligopeptide from SMN exon 2. AbSMN immunostaining in neuroblastoma cells and mouse and human central nervous system (CNS)(More)