Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical and experimental studies clearly demonstrate that prolonged seizures and status epilepticus induce neuronal cell death in the brain. Recent evidence suggests that induction of apoptosis contributes greatly to seizure-induced brain damage. We recently demonstrated that intrahippocampal delivery of botulinum neurotoxin E (BoNT/E) in the rat hippocampus is able to prevent neuronal loss, which occurs after kainic-acid-induced seizures. Here, we investigated the molecular mechanisms of BoNT/E-mediated neuroprotection. We found that intrahippocampal administration of BoNT/E prevents the upregulation of apoptotic proteins (phosphorylated c-Jun and cleaved caspase 3), which occurs in hippocampal neurones following kainic acid seizures. These results demonstrate that the neuroprotective action of BoNT/E on seizure-injured hippocampal neurons involves the blockade of well-characterized apoptotic pathways.
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PMID:BoNT/E prevents seizure-induced activation of caspase 3 in the rat hippocampus. 1741 60

Clinical and experimental studies clearly demonstrate that prolonged seizures and status epilepticus induce neuronal cell death in the brain. Recent evidence suggests that induction of apoptosis contributes greatly to seizure-induced brain damage. We recently demonstrated that intrahippocampal delivery of botulinum neurotoxin E (BoNT/E) in the rat hippocampus is able to prevent neuronal loss, which occurs after kainic-acid-induced seizures. Here, we investigated the molecular mechanisms of BoNT/E-mediated neuroprotection. We found that intrahippocampal administration of BoNT/E prevents the upregulation of apoptotic proteins (phosphorylated c-Jun and cleaved caspase 3), which occurs in hippocampal neurones following kainic acid seizures. These results demonstrate that the neuroprotective action of BoNT/E on seizure-injured hippocampal neurons involves the blockade of well-characterized apoptotic pathways.
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PMID:BoNT/E prevents seizure-induced activation of caspase 3 in the rat hippocampus. 1744 Dec 89

Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 +/- 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p < 0.01), but cleaved caspase-9 and caspase-3 showed no significant changes in either group. TEM findings showed irreversible and reversible inner-structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.
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PMID:Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle. 2052 64

Botulinum neurotoxins (BoNTs) block the release of a series of neurotransmitters, which are pivotal for neuron action. Intrahippocampal administration of BoNTs inhibits glutamate release, protects neurons against cell death, and attenuates epileptic seizures. Compared with intrahippocampal administration, intranasal delivery is less invasive and more practical for chronic drug administration. To assess whether intranasal administration is feasible, we examined the role of botulinum neurotoxin A (BoNT/A) in hippocampal neuronal injury after status epilepticus (SE) induced by pilocarpine. Our data showed BoNT/A could bypass the blood-brain barrier (BBB) and entered the olfactory bulb and hippocampal neurons. In addition, SE could result in up-regulation of pro-apoptotic proteins (Caspase-3, Bax), down-regulation of anti-apoptotic protein Bcl-2 and neuronal death in hippocampus. BoNT/A could suppress the expression of Caspase-3 and Bax, attenuate the decrease of Bcl-2, and inhibit hippocampal neuron death induced by SE. Meanwhile, there was no significant difference in cognitive behavior between the BoNT/A-pretreated rats and normal rats. Thus, we provided a more convenient and less invasive route for taking advantage of BoNT/A in the field of anti-epilepsy.
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PMID:Intranasal Delivery of Botulinum Neurotoxin A Protects against Hippocampal Neuron Death in the Lithium-Pilocarpine Rat Model. 3087 18