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Novel Targets for Developing Antiseizure and Potentially Antiepileptogenic Drugs

机译:开发抗癫痫药和潜在的抗癫痫药的新目标

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摘要

Epilepsy is a chronic neurological disorder caused by abnormal changes in the functions of neuronal circuits and manifested by seizures. It affects patients of all age, substantially worsens the quality of life for the patients as well as their families, and imposes a huge economic burden on the healthcare system. Historically, efforts for discovering and developing antiseizure therapies have been focused on modulating the functions of receptors, transporters, and enzymes expressed by neurons. These drug development efforts have paid off, as we have over 25 antiseizure drugs available in the clinic. However, these drugs mainly provide symptomatic relief from seizures and often cause serious adverse effects. Importantly, almost one-third of patients with epilepsy do not have their seizures adequately controlled by available drugs. To address this problem, researchers are investigating cellular and molecular mechanisms fundamental to the optimal function of neuronal circuits. Evidence shows that disruptions in these mechanisms cause impairment in neuroglial interactions, uncontrolled inflammation, aberrant synaptogenesis, and neurodegeneration in genetic and acquired epilepsies. Many novel therapeutic targets have been identified to target these mechanisms for developing new antiseizure drugs. In addition, the field is exploring new drug targets which may impede the development of epilepsy. We have summarized some of these novel targets in this brief review.
机译:癫痫病是一种慢性神经系统疾病,由神经元回路功能的异常变化引起,并表现为癫痫发作。它影响所有年龄的患者,大大恶化患者及其家人的生活质量,并给医疗系统带来巨大的经济负担。从历史上看,发现和开发抗癫痫疗法的努力一直集中在调节神经元表达的受体,转运蛋白和酶的功能上。这些药物开发的努力已获得回报,因为我们诊所有超过25种抗癫痫药。但是,这些药物主要可缓解癫痫症状,并经常引起严重的不良反应。重要的是,近三分之一的癫痫患者的癫痫发作没有被可用药物充分控制。为了解决这个问题,研究人员正在研究对神经回路的最佳功能至关重要的细胞和分子机制。有证据表明,这些机制的破坏会导致遗传性和获得性癫痫的神经胶质相互作用受损,炎症不受控制,突触异常发生以及神经变性。已经鉴定出许多新颖的治疗靶标以靶向这些机制以开发新的抗癫痫药。另外,该领域正在探索可能阻碍癫痫发展的新药物靶标。在这篇简短的评论中,我们总结了其中一些新颖的目标。

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