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The transcription factor NF-kappaB is expressed in neurons wherein it is activated in response to a variety of stress- and injury-related stimuli including exposure to cytokines such as tumor necrosis factor-alpha (TNFalpha), and excitotoxic and oxidative insults. NF-kappaB may play a role in the anti-death actions of TNFalpha in cultured hippocampal(More)
Steroid hormones, particularly estrogens and glucocorticoids, may play roles in the pathogenesis of neurodegenerative disorders, but their mechanisms of action are not known. We report that estrogens protect cultured hippocampal neurons against glutamate toxicity, glucose deprivation, FeSO4 toxicity, and amyloid beta-peptide (A beta) toxicity. The toxicity(More)
In Alzheimer disease (AD) the amyloid beta-peptide (A beta) accumulates in plaques in the brain. A beta can be neurotoxic by a mechanism involving induction of reactive oxygen species (ROS) and elevation of intracellular free calcium levels ([Ca2+]i). In light of evidence for an inflammatory response in the brain in AD and reports of increased levels of(More)
Alternative processing of the beta-amyloid precursor protein (beta APP) can result in liberation of either secreted forms of beta APP (APPSs), which may play roles in neuronal plasticity and survival, or amyloid beta-peptide (A beta), which can be neurotoxic. In rat hippocampal cell cultures A beta 1-40 caused a time- and concentration-dependent reduction(More)
The excitatory neurotransmitter glutamate is believed to play important roles in development, synaptic plasticity, and neurodegenerative conditions. Recent studies have shown that neurotrophic factors can modulate neuronal excitability and survival and neurite outgrowth responses to glutamate, but the mechanisms are unknown. The present study tested the(More)
The amyloid beta-peptide (A beta) that accumulates as insoluble plaques in the brains of Alzheimer's victims can be neurotoxic, by a mechanism that may involve generation of reactive oxygen species (ROS) and destabilization of cellular calcium homeostasis. We now provide evidence that the mechanism of neurotoxicity of two other amyloidogenic peptides (APs),(More)
Potassium channel openers (KCOs) such as diazoxide and levochromakalim can protect cardiac myocytes against ischemic injury and neurons against excitotoxic injury, presumably because of their ability to hyperpolarize the plasma membrane and reduce calcium influx. We now report that diazoxide, levocromakalim (LCC), and to a lesser extent pinacidil, protect(More)
Neurotrophin-4/5 (NT-4/5) is a recently discovered member of the neurotrophin family of neurotrophic factors which includes NGF, BDNF and NT-3. NT-4/5 is expressed in the brain where its function is unknown. We have found that NT-4/5 can protect cultured embryonic rat hippocampal and cortical neurons against glucose deprivation-induced injury. Significant(More)
The transcription factor NF kappa B is activated by various signals associated with brain injury, including tumor necrosis factor (TNF), oxidative insults, and amyloid beta-peptide (A beta). We recently reported that TNFs activate NF kappa B in neurons and protect them against excitotoxic and oxidative insults, including A beta toxicity. We now report that(More)
Uric acid is a well-known natural antioxidant present in fluids and tissues throughout the body. Oxyradical production and cellular calcium overload are believed to contribute to the damage and death of neurons that occurs following cerebral ischemia in victims of stroke. We now report that uric acid protects cultured rat hippocampal neurons against cell(More)