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Human neuronal nicotinic acetylcholine receptor (AChR) alpha4 subunits and an alpha4 mutant (S247Falpha4) found in autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) were expressed along with beta2 in permanently transfected tsA201 human embryonic kidney cell lines. Their sensitivity to activation, desensitization, and up-regulation by cholinergic(More)
Uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists with fast off-rate (UFO) may represent promising drug candidates for various neurodegenerative disorders. In this study, we report that bis(propyl)-cognitin, a novel dimeric acetylcholinesterase inhibitor and gamma-aminobutyric acid subtype A receptor antagonist, is such an antagonist of NMDA(More)
The neuroprotective properties of bis(7)-tacrine, a novel dimeric acetylcholinesterase (AChE) inhibitor, on glutamate-induced excitotoxicity were investigated in primary cultured cerebellar granule neurons (CGNs). Exposure of CGNs to 75 mum glutamate resulted in neuronal apoptosis as demonstrated by Hoechst staining, TUNEL, and DNA fragmentation assays. The(More)
The excessive activation of the N-methyl-D-aspartate receptor (NMDAR)/nitric oxide (NO) pathway has been proposed to be involved in the neuropathology of various neurodegenerative disorders. In this study, NO was found to mediate glutamate-induced excitotoxicity in primary cultured neurons. Compared with the NO synthase (NOS) inhibitor,(More)
Beta amyloid protein (Abeta) and acetylcholinesterase (AChE) have been shown to be closely implicated in the pathogenesis of Alzheimer's disease. In the current study, we investigated the effects of bis(7)-tacrine, a novel dimeric AChE inhibitor, on Abeta-induced neurotoxicity in primary cortical neurons. Bis(7)-tacrine, but not other AChE inhibitors,(More)
Somatosensory neurons mediate our sense of touch. They are critically involved in transducing pain and itch sensations under physiological and pathological conditions, along with other skin-resident cells. Tissue damage and inflammation can produce a localized or systemic sensitization of our senses of pain and itch, which can facilitate our detection of(More)
Oxidative stress-induced apoptosis plays a critical role in the pathogenesis of various neurodegenerative disorders. In this study, the neuroprotective properties of bis(12)-hupyridone (B12H), a novel dimeric acetylcholinesterase (AChE) inhibitor modified from a naturally occurring monomeric analogue, huperzine A, on H₂O₂-induced neurotoxicity were(More)
Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise(More)
BACKGROUND AND PURPOSE Retinoids, through their activation of retinoic acid receptors (RARs) and retinoid X receptors, regulate diverse cellular processes, and pharmacological intervention in their actions has been successful in the treatment of skin disorders and cancers. Despite the many beneficial effects, administration of retinoids causes irritating(More)
Chronic pain affects billions of lives globally and is a major public health problem in the United States. However, pain management is still a challenging task due to a lack of understanding of the fundamental mechanisms of pain. In the past decades transient receptor potential (TRP) channels have been identified as molecular sensors of tissue damage and(More)