Dr. B.R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, New Delhi, India.
Department of Biophysics, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Expert Opin Ther Targets. 2024 Apr;28(4):283-294. doi: 10.1080/14728222.2024.2343952. Epub 2024 Apr 21.
Epilepsy is a chronic neurological condition characterized by a persistent propensity for seizure generation. About one-third of patients do not achieve seizure control with the first-line treatment options, which include >20 antiseizure medications. It is therefore imperative that new medications with novel targets and mechanisms of action are developed.
Clinical studies and preclinical research increasingly implicate Non-receptor tyrosine kinases (nRTKs) in the pathogenesis of epilepsy. To date, several nRTK members have been linked to processes relevant to the development of epilepsy. Therefore, in this review, we provide insight into the molecular mechanisms by which the various nRTK subfamilies can contribute to the pathogenesis of epilepsy. We further highlight the prospective use of specific nRTK inhibitors in the treatment of epilepsy deriving evidence from existing literature providing a rationale for their use as therapeutic targets.
Specific small-molecule inhibitors of NRTKs can be employed for the targeted therapy as already seen in other diseases by examining the precise molecular pathways regulated by them contributing to the development of epilepsy. However, the evidence supporting NRTKs as therapeutic targets are limiting in nature thus, necessitating more research to fully comprehend their function in the development and propagation of seizures.
癫痫是一种慢性神经系统疾病,其特征是持续存在癫痫发作的倾向。大约三分之一的患者无法通过一线治疗选择(包括>20 种抗癫痫药物)控制癫痫发作。因此,开发具有新靶点和作用机制的新药迫在眉睫。
临床研究和临床前研究越来越多地表明非受体酪氨酸激酶(nRTK)在癫痫发病机制中起作用。迄今为止,已有几种 nRTK 成员与与癫痫发生相关的过程有关。因此,在这篇综述中,我们深入了解了各种 nRTK 亚家族通过哪些分子机制有助于癫痫的发病机制。我们进一步强调了特定 nRTK 抑制剂在治疗癫痫中的潜在用途,从现有文献中提供了使用它们作为治疗靶点的理由。
通过检查调节癫痫发生的精确分子途径,可将特定的 NRTK 小分子抑制剂用于靶向治疗,就像在其他疾病中已经看到的那样。然而,支持 NRTK 作为治疗靶点的证据本质上是有限的,因此需要更多的研究来充分理解它们在癫痫发作的发展和传播中的作用。