Abstract:
:Among the diverse sets of nicotinic acetylcholine receptors (nAChRs), the alpha7 subtype is highly expressed in the hippocampus and cortex and is thought to play important roles in a variety of cognitive processes. In this review, we describe the properties of a novel biaryl diamine alpha7 nAChR agonist, A-582941. A-582941 was found to exhibit high-affinity binding and partial agonism at alpha7 nAChRs, with acceptable pharmacokinetic properties and excellent distribution to the central nervous system (CNS). In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation. A-582941 enhanced cognitive performance in behavioral models that capture domains of working memory, short-term recognition memory, memory consolidation, and sensory gating deficit. A-582941 exhibited a benign secondary pharmacodynamic and tolerability profile as assessed in a battery of assays of cardiovascular, gastrointestinal, and CNS function. The studies summarized in this review collectively provide preclinical validation that alpha7 nAChR agonism offers a mechanism with potential to improve cognitive deficits associated with various neurodegenerative and psychiatric disorders.
journal_name
CNS Neurosci Therjournal_title
CNS neuroscience & therapeuticsauthors
Tietje KR,Anderson DJ,Bitner RS,Blomme EA,Brackemeyer PJ,Briggs CA,Browman KE,Bury D,Curzon P,Drescher KU,Frost JM,Fryer RM,Fox GB,Gronlien JH,Håkerud M,Gubbins EJ,Halm S,Harris R,Helfrich RJ,Kohlhaas KL,Law D,Mdoi
10.1111/j.1527-3458.2008.00037.xsubject
Has Abstractpub_date
2008-04-01 00:00:00pages
65-82issue
1eissn
1755-5930issn
1755-5949pii
CNS037journal_volume
14pub_type
杂志文章,评审abstract:AIMS:In this study, we examined the expression of GINS2 in glioma and determined its role in glioma development. METHODS:The protein expression of GINS2 was assessed in 120 human glioma samples via immunohistochemistry. Then, we suppressed the expression of GINS2 in glioma cell strains U87 and U251 using a short hairp...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.13064
更新日期:2019-02-01 00:00:00
abstract::Depression is the leading cause of disability around the world, but little is known about its pathology. Currently, the diagnosis of depression is made based on clinical manifestations, with little objective evidence. Magnetic resonance imaging (MRI) has been used to investigate the pathological changes in brain anato...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/cns.12835
更新日期:2018-11-01 00:00:00
abstract:AIMS:The MS-275 is a selective inhibitor of class I histone deacetylases (HDACs), which has been reported as a potential strategy in some central nervous system diseases associated with neurodegeneration and disturbed learning. However, its role in traumatic brain injury is not well defined. In this study, we examined ...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,收录出版
doi:10.1111/cns.12082
更新日期:2013-05-01 00:00:00
abstract:AIMS:Accumulated evidence indicates that cerebral metabolic features, evaluated by proton magnetic resonance spectroscopy (1 H-MRS), are sensitive to early mitochondrion dysfunction associated with mitochondrial encephalomyopathy (ME). The metabolite ratios of lactate (lac)/Cr, N-acetyl aspartate (NAA)/creatine (Cr), t...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12714
更新日期:2017-08-01 00:00:00
abstract::Fingolimod is a sphingosine 1-phosphate (S1P) receptor modulator approved to treat relapsing-remitting multiple sclerosis (MS). Initiation of treatment with fingolimod has been found to produce transient bradycardia and/or slowing of atrioventricular impulse conduction in a small proportion of patients. This effect is...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/cns.12283
更新日期:2014-06-01 00:00:00
abstract::Post-traumatic stress disorder (PTSD) has become a global health issue, with prevalence rates ranging from 1.3% to 37.4%. As there is little current data on PTSD in Canada, an epidemiological study was conducted examining PTSD and related comorbid conditions. Modified versions of the Composite International Diagnostic...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/j.1755-5949.2008.00049.x
更新日期:2008-10-01 00:00:00
abstract::Octodon degus (O. degus) is a diurnal rodent that spontaneously develops several physiopathological conditions, analogous in many cases to those experienced by humans. In light of this, O. degus has recently been identified as a very valuable animal model for research in several medical fields, especially those concer...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/cns.12125
更新日期:2013-09-01 00:00:00
abstract:AIMS:The mouse model of allo-head and body reconstruction (AHBR) has recently been established to further the clinical development of this strategy for patients who are suffering from mortal bodily trauma or disease, yet whose mind remains healthy. Animal model studies are indispensable for developing such novel surgic...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12422
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Activated microglia-mediated inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). In addition, chronic activation of NLRP3 inflammasomes triggered by amyloid β peptide (Aβ) in microglia contributes to persistent neuroinflammation. Here, the primary goal was to assess whether Dihydro...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12983
更新日期:2018-12-01 00:00:00
abstract:AIMS:Blood-borne monocytes/macrophages infiltrate the brain in massive numbers after ischemic stroke, but their impact on poststroke brain injury and recovery remains elusive. This study examined the transcriptomic changes in monocytes/macrophages after ischemic stroke and the functional implications of these changes, ...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.13256
更新日期:2019-12-01 00:00:00
abstract:AIMS:Intracellular calcium plays an important role in neuronal hyperexcitability that leads to seizures. One calcium influx route of interest is the transient receptor potential vanilloid type 1 (TRPV1) channel. Here, we evaluated the effects of capsazepine (CPZ), a potent blocker of TRPV1 channels on acoustically evok...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12770
更新日期:2018-01-01 00:00:00
abstract:AIMS:Prior studies have demonstrated the involvement of leptin and cannabinoids in food intake and metabolism. However, the interaction between leptin and cannabinoids in epilepsy has not been studied. This study elucidated the relationship between leptin and cannabinoids in penicillin-induced epileptiform activity in ...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12075
更新日期:2013-04-01 00:00:00
abstract::Retinal degenerative diseases (RDs) such as retinitis pigmentosa (RP) are a genetically heterogeneous group of disorders characterized by night blindness and peripheral vision loss, which caused by the dysfunction and death of photoreceptor cells. Although many causative gene mutations have been reported, the final co...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/cns.12471
更新日期:2016-01-01 00:00:00
abstract::Status epilepticus (SE), a neurological emergency both in adults and in children, could lead to brain damage and even death if untreated. Generalized convulsive SE (GCSE) is the most common and severe form, an example of which is that induced by organophosphorus nerve agents. First- and second-line pharmacotherapies a...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/cns.12096
更新日期:2013-06-01 00:00:00
abstract::Tau, the microtubule-associated protein, forms insoluble filaments that accumulate as neurofibrillary tangles in Alzheimer's disease (AD) and related tauopathies. Under physiological conditions, tau regulates the assembly and maintenance of the structural stability of microtubules. In the diseased brain, however, tau ...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/j.1755-5949.2010.00177.x
更新日期:2011-10-01 00:00:00
abstract::Neurodegenerative diseases result from the gradual and progressive loss of neural cells and lead to nervous system dysfunction. The rapidly advancing stem cell field is providing attractive alternative options for fighting these diseases. Results have provided proof of principle that cell replacement can work in human...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/j.1755-5949.2011.00239.x
更新日期:2012-02-01 00:00:00
abstract:AIMS:Exposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose-lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH e...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.13186
更新日期:2020-01-01 00:00:00
abstract:AIMS:To examine whether early rise of neutrophil-to-lymphocyte ratio (NLR) after patient hospitalization correlates with 30-day mortality in patients with spontaneous intracerebral hemorrhage (ICH). METHODS:This retrospective study included all patients receiving treatment for spontaneous ICH between January 2015 and ...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12977
更新日期:2019-01-01 00:00:00
abstract:AIMS:Axonal degeneration is a pathological symbol in the early stage of Alzheimer's disease (AD), which can be triggered by amyloid-β (Aβ) peptide deposition. Growing evidence indicates that deficit of autophagy eventually leads to the axonal degeneration. Our previous studies have shown that Dendrobium nobile Lindl al...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12678
更新日期:2017-04-01 00:00:00
abstract:AIMS:To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) on motor recovery after stroke using a prospective, double-blind, randomized, sham-controlled study. METHODS:Patients with unilateral subcortical infarction in the middle cerebral artery territory within 1 week after onset were e...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1111/cns.12762
更新日期:2017-12-01 00:00:00
abstract::Cysteinyl leukotrienes are a group of the inflammatory lipid molecules well known as mediators of inflammatory signaling in the allergic diseases. Although they are traditionally known for their role in allergic asthma, allergic rhinitis, and others, recent advances in the field of biomedical research highlighted the ...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/cns.12596
更新日期:2016-12-01 00:00:00
abstract:AIM:To compare atomoxetine (ATX) length of therapy (LoT) among adults with ADHD who reached the recommended dose of 80 mg/day (ATX ≥ 80) versus those who did not (ATX < 80) analyzed separately in patients prescribed ATX as monotherapy (mono) and in combination with other ADHD medications (combo). METHODS:This was a re...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12595
更新日期:2016-12-01 00:00:00
abstract:AIMS:This study investigated the influence of sigma-1 receptor (σ1 R) deficiency on adult neurogenesis. METHODS:We employed 8-week-old male σ1 R knockout (σ1 R(-/-) ) mice to examine the proliferation and differentiation of progenitor cells, and the survival and neurite growth of newborn neurons in hippocampal dentate...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12129
更新日期:2013-09-01 00:00:00
abstract:AIM:Multiple sclerosis (MS) is a neurological autoimmune disorder characterized by mistaken attacks of inflammatory cells against the central nervous system (CNS), resulting in demyelination and axonal damage. Kv1.3 channel blockers can inhibit T-cell activation and have been designed for MS therapy. However, little is...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12848
更新日期:2018-10-01 00:00:00
abstract::Cerebral ischemia is a severe outcome that could cause cognitive and motor dysfunction, neurodegenerative diseases and even acute death. Although the existence of autophagy in cerebral ischemia is undisputable, the consensus has not yet been reached regarding the exact functions and influence of autophagy in cerebral ...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/cns.12005
更新日期:2012-11-01 00:00:00
abstract:INTRODUCTION:Patients with temporal lobe epilepsy (TLE) often suffer from comorbid psychiatric diagnoses such as depression, anxiety, or impaired cognitive performance. Endocannabinoid (eCB) signaling is a key regulator of synaptic neurotransmission and has been implicated in the mechanisms of epilepsy as well as sever...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12302
更新日期:2014-10-01 00:00:00
abstract:INTRODUCTION:miRNAs dysregulate in spinal cord injury (SCI) and have been demonstrated to play a crucial role in neurite outgrowth. However, the underlying mechanism remains elusive. In this study, we constructed a mouse model of SCI, extracted RNA from injured spinal cord tissue for the use of microarray assay. miR-18...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12761
更新日期:2017-11-01 00:00:00
abstract::Patients with neurodegenerative disease frequently experience hallucinations and illusionary perceptions. As early symptoms, hallucinations may even have diagnostic relevance (i.e., for the diagnosis of Lewy Body Dementia). In the later course of the disease, hallucinations may appear as characteristic symptoms and of...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
doi:10.1111/j.1755-5949.2011.00247.x
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVE:To evaluate the cognitive function of Chinese patients with Parkinson's disease PD postsubthalamic nucleus deep brain stimulation (STN-DBS). METHODS:Cognitive function was assessed by neuropsychological methods in PD patients. Twenty matched healthy persons served as normal controls. t test, analysis of vari...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.13392
更新日期:2020-09-01 00:00:00
abstract:AIMS:To evaluate the health-related quality of life (HRQL) and its correlates in children and adolescents with narcolepsy. METHODS:We compared the clinical characteristics of control subjects and patients with primary narcolepsy from data collected at the National Reference Centers for Narcolepsy. RESULTS:The cohort ...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
doi:10.1111/cns.12291
更新日期:2014-08-01 00:00:00