کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
946432 | 926193 | 2008 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease
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کلمات کلیدی
Acetylcholine - استیل کولینAlzheimer's disease - بیماری آلزایمرMemory - حافظهDopamine - دوپامینCognition - شناختBehavioral symptoms - علائم رفتاریneural cell adhesion molecule - مولکول چسبندگی سلولی عصبیnorepinephrine - نوراپی نفرینSynaptic plasticity - پلاستیسیته سیناپسیglutamate - گلوتاماتLearning - یادگیری
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
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چکیده انگلیسی
Alzheimer's disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive performance accompanied by behavioral and psychological syndromes, such as depression and psychosis. The neurochemical correlates of these clinical manifestations now appear to involve dysfunctions of multiple neurotransmitter pathways. Because of the extensive serotonergic denervation that has been observed in the AD brain and the important role played by serotonin (5-HT) in both cognition and behavioral control, this neurotransmitter system has become a focus of concerted research efforts to identify new treatments for AD. 5-HT exerts its diverse physiological and pharmacological effects through actions on multiple receptor subtypes. One of the newest members of this family is the 5-HT6 receptor, a subtype localized almost exclusively in the CNS, predominating in brain regions associated with cognition and behavior. With the subsequent development of selective 5-HT6 receptor antagonists, preclinical studies in rodents and primates have elucidated the function of this receptor subtype in more detail. It is increasingly clear that blockade of 5-HT6 receptors leads to an improvement of cognitive performance in a wide variety of learning and memory paradigms and also results in anxiolytic and antidepressant-like activity. These actions are largely underpinned by enhancements of cholinergic, glutamatergic, noradrenergic, and dopaminergic neurotransmission, together with learning-associated neuronal remodeling. A preliminary report that the cognitive enhancing properties of a 5-HT6 receptor antagonist (namely, SB-742457) extends into AD sufferers further highlights the therapeutic promise of this mechanistic approach.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurotherapeutics - Volume 5, Issue 3, July 2008, Pages 458-469
Journal: Neurotherapeutics - Volume 5, Issue 3, July 2008, Pages 458-469
نویسندگان
Neil Upton, Tsu Tshen Chuang, Ann J. Hunter, David J. Virley,