Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diazepam binding inhibitor (DBI) and its processing products are endogenous modulators of GABAA and linked to various brain disorders ranging from anxiety and drug dependence to epilepsy. To investigate the physiological role of endogenously expressed DBI in the brain we created a transgenic mouse line overexpressing DBI gene. Transgenic mice had a 37x increased protein expression and immunohistochemistry showed excessive glial expression in the infragranular region of the dentate gyrus. Transgenic animals had significantly larger lateral ventricles and decreased plasticity of excitatory synapses without affecting either inhibitory or excitatory synaptic transmission. In behavioral tests transgenic animals had no differences in motor and exploratory activity, yet impaired hippocampus-dependent learning and memory. Overexpression did not cause anxiety or proconflict behavior, nor influenced kainic acid or pentylenetetrazole induced seizure activity. Our transgenic mouse line demonstrates that endogenously overexpressed DBI impairs hippocampus-dependent learning without anxiety or proconflict behavior.
Mol Cell Neurosci 2007 Feb
PMID:Diazepam binding inhibitor overexpression in mice causes hydrocephalus, decreases plasticity in excitatory synapses and impairs hippocampus-dependent learning. 1715 Mar 71

Drug dependence (DD) is commonly co-morbid with alcohol dependence (AD). Many studies have also shown common genetic risk factors for these disorders. We previously reported associations of AD with seven alcohol dehydrogenase (ADH) genes. The present study examines the relationship between these genes and DD. We genotyped 16 markers within the ADH gene cluster and 38 unlinked ancestry-informative markers in a case-control sample of 718 individuals. All markers were consistent with Hardy-Weinberg equilibrium in controls, but some markers showed Hardy-Weinberg disequilibrium in cases (minimal P = 0.002). Genotypes of many markers were associated with DD, both before and after controlling for admixture effects (minimal P < 1.0 x 10(-6)). Diplotype trend regression analysis showed that ADH5 and ADH6 genotypes, and diplotypes at ADH1A, ADH1B, ADH1C and ADH7 (minimal P = 0.002), were associated with DD in European-Americans and/or African-Americans. This first report of an allelic association of these loci with DD provides new insight into the mechanism of genetic risk for DD. These findings, obtained using a series of powerful and reliable analytic methods, may also help to explain the high rate of co-morbidity between AD and DD.
Hum Mol Genet 2007 Feb 15
PMID:Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans. 1718 88

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21-23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29-31, 2007).
Mol Pain 2006 Dec 30
PMID:Recent advances in basic neurosciences and brain disease: from synapses to behavior. 1719 11

Animal models in the field of addiction are considered to be among the best available models of neuropsychiatric disease. These models have undergone a number of refinements that allow deeper understanding of the circuitry involved in initiating drug seeking and relapse. Notably, the demonstrable involvement of classic corticostriatal habit circuitry and the engagement of prefrontal cortical circuits in extinction training may have relevance to the therapeutic modulation of habit circuitry and drug addiction in humans.
Mol Interv 2006 Dec
PMID:Animal models and brain circuits in drug addiction. 1720 Apr 61

The CB1 cannabinoid receptors are among the most highly expressed G protein coupled receptors (GPCRs) in the brain. Their activation has been associated with a wide range of behaviors, including cognition, pain perception, drug addiction, and memory consolidation, and they have been pharmaceutically targeted for pain therapies, smoking cessation, and appetite control. The CB1 receptor has been challenging to study at the molecular level given the hydrophobic nature of its lipid-based agonists and difficulties expressing the recombinant cDNA in cellular cultures. Early transfection studies in cell cultures revealed predominantly intracellular localization of the CB1 receptor and it was not clear whether this was the "normal" distribution or whether this was some artifact of the cellular model systems. However, studies of the endogenously expressed CB1 receptors using specific antibodies have shown that the there is usually a distinct intracellular, vesicular localization of the CB1 receptor. Confocal microscopy analysis reveals that the intracellular CB1 receptors are localized to vesicles, which implies that the receptors are "trafficking" or undergoing a continuous cycle of internalization and membrane relocalization. The article by McDonald et al. (p. 976) in this issue of Molecular Pharmacology addresses whether this constitutive trafficking is related to the activation state of the receptor and whether it plays a role in axonal versus somatodendritic receptor localization.
Mol Pharmacol 2007 Apr
PMID:Constitutive trafficking--more than just running in circles? 1725 27

The advent of the highly selective cannabinoid receptor (CB1) antagonist, rimonabant (SR141716; Acomplia) can revolutionize the ability of the clinicians to manage obesity. Large-scale clinical trials have demonstrated that rimonabant therapy can reduce obesity. Although, the precise mechanisms of action of rimonabant have to be further dissected, it is emerging, from both preclinical and clinical research, that not only is rimonabant an antiobesity drug, but also its pleiotropic functions affect a broad range of diseases, from obesity-related comorbidities to drug dependence and cancer. Here we review recent data from the literature and discuss the full pharmacological potential of this drug.
Mol Pharmacol 2007 Jun
PMID:Rimonabant: just an antiobesity drug? Current evidence on its pleiotropic effects. 1732 63

The tetrahydroprotoberberines (THPBs) are compounds isolated from Chinese herbs that possess a unique pharmacological profile as D2 dopamine receptor antagonists and D1 receptor agonists. l-Tetrahydropalmatine (l-THP) and l-stepholidine (SPD), members of the THPB family, were shown to have potential clinical use in the treatment of pain. However, their mechanism of action is not clear. In the past decades, Chinese scientists have made a great deal of effort to explore the mechanisms by which the THPBs and its analogues elicit antinociception and their potential utility in treating drug abuse. It is now clear that the antinociception produced by l-THP is related to inhibition of D(2) dopamine receptors. The present review focuses on the recent progress made in understanding the mechanisms of l-THP- and l-SPD-mediated antinociception and the sequel of drug addiction.
Cell Mol Neurobiol 2008 Jun
PMID:Recent development in studies of tetrahydroprotoberberines: mechanism in antinociception and drug addiction. 1771 May 33

Drug addiction, characterized by high rates of relapse, is recognized as a kind of neuroadaptive disorder. Since the extracellular signal-regulated kinase (ERK) pathway is critical to neuroplasticity in the adult brain, understanding the role this pathway plays is important for understanding the molecular mechanism underlying drug addiction and relapse. Here, we review previous literatures that focus on the effects of exposure to cocaine, amphetamine, Delta(9)-tetrahydrocannabinol (THC), nicotine, morphine, and alcohol on ERK signaling in the mesocorticolimbic dopamine system; these alterations of ERK signaling have been thought to contribute to the drug's rewarding effects and to the long-term maladaptation induced by drug abuse. We then discuss the possible upstreams of the ERK signaling pathway activated by exposure of drugs of abuse and the environmental cues previously paired with drugs. Finally, we argue that since ERK activation is a key molecular process in reinstatement of conditioned place preference and drug self-administration, the pharmacological manipulation of the ERK pathway is a potential treatment strategy for drug addiction.
Cell Mol Neurobiol 2008 Feb
PMID:Drug-induced alterations in the extracellular signal-regulated kinase (ERK) signalling pathway: implications for reinforcement and reinstatement. 1804 76

Neuroscience research in China has undergone rapid expansion since 1980. The Neuroscience Research Institute of Peking University, one of the most active neuroscience research groups in China, was founded in 1987. Currently, the institute is overseeing four research areas, i.e., (1) pain and analgesia, (2) drug abuse and acupuncture treatment for drug addiction, (3) the mechanism of neurological degenerative disorders, and (4) the role of neuroglia in central nervous system injury. The institute is simultaneously investigating both theoretical and clinical studies. Acupuncture remains the core of research, while pain and drug abuse form the two disciplines.
Cell Mol Neurobiol 2008 Jan
PMID:The Neuroscience Research Institute at Peking University: a place for the solution of pain and drug abuse. 1805 18

In recent years, Chinese neuropharmacologists have done a lot of basic and practical work in neuropharmacology, especially in the fields of pain, drug dependence, depression, Alzheimer's disease, schizophrenia, having obtained some exciting results that are of great significance for the development of neuropharmacology. Here I would like to review recent progress in the research fields of neuropharmacology in China.
Cell Mol Neurobiol 2008 Feb
PMID:Recent progress in the research field of neuropharmacology in China. 1824 16


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