Stephen Brimijoin

Yang Gao16
Marilyn E Carroll4
Liyi Geng4
16Yang Gao
4Marilyn E Carroll
4Liyi Geng
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Successive rational mutations of human butyrylcholinesterase (BChE) followed by fusion to human serum albumin have yielded an efficient hydrolase that offers realistic options for therapy of cocaine overdose and abuse. This albumin-BChE prevented seizures in rats given a normally lethal cocaine injection (100 mg/kg, i.p.), lowered brain cocaine levels even(More)
Current mouse models of Alzheimer's disease show brain pathology that correlates to a degree with memory impairment, but underlying molecular mechanisms remained unknown. Here we report studies with three lines of transgenic mice: animals that doubly express mutated human amyloid precursor protein (APPswe) and human acetylcholinesterase (hAChE); and animals(More)
Aphids, among the most destructive insects to world agriculture, are mainly controlled by organophosphate insecticides that disable the catalytic serine residue of acetylcholinesterase (AChE). Because these agents also affect vertebrate AChEs, they are toxic to non-target species including humans and birds. We previously reported that a cysteine residue(More)
New insecticides are urgently needed because resistance to current insecticides allows resurgence of disease-transmitting mosquitoes while concerns for human toxicity from current compounds are growing. We previously reported the finding of a free cysteine (Cys) residue at the entrance of the active site of acetylcholinesterase (AChE) in some insects but(More)
Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for(More)
Treatment of Alzheimer's disease has been dominated by the use of acetylcholinesterase (AChE) inhibitors. These drugs compensate for the death of cholinergic neurons and offer symptomatic relief by inhibiting acetylcholine (ACh) turnover and restoring synaptic levels of this neurotransmitter. Recently, however, AChE itself has been implicated in the(More)
We previously found that a quadruple mutant cocaine hydrolase derived from human butyrylcholinesterase [termed cocaine esterase (CocE)] can suppress or reverse cocaine toxicity and abolish drug-primed reinstatement in rats. Here, we examined whether gene transfer of CocE reduces cocaine actions in brain reward centers. Early experiments used a standard,(More)
BACKGROUND Cocaine dependence is a pervasive disorder with high rates of relapse. In a previous study, direct administration of a quadruple mutant albumin-fused butyrylcholinesterase that efficiently catalyzes hydrolysis of cocaine to benzoic acid and ecgonine methyl ester acutely blocked cocaine seeking in an animal model of relapse. In the present(More)
To clarify the role of Angiotensin II in the regulation of peripheral sensory and motor systems, we initiated a study of the expression, localization and transport of Angiotensin II receptor types in the rat sciatic nerve pathway, including L(4)-L(5) spinal cord segments, the corresponding dorsal root ganglia (DRGs) and the sciatic nerve. We used(More)
There is increasing evidence that human plasma butyrylcholinesterase can lower the toxicity of cocaine overdose. Recently, with structure-based protein engineering, we converted this enzyme into a more efficient cocaine hydrolase (CocE). When tested in rats, CocE shortened cocaine's plasma half-life and decreased drug accumulation in heart and brain. Here,(More)