Forcelli Patrick A
Department of Pharmacology & Physiology, Georgetown University, Washington, DC, USA.
Department of Neuroscience, Georgetown University, Washington, DC, USA.
Epilepsy Curr. 2022 Sep 19;22(5):303-308. doi: 10.1177/15357597221120348. eCollection 2022 Sep-Oct.
The fundamental commonality across pharmacotherapies for the epilepsies is the modulation of neuronal excitability. This poses a clear challenge-patterned neuronal excitation is essential to normal function, thus disrupting this activity leads to side effects. Moreover, the efficacy of current pharmacotherapy remains incomplete despite decades of drug development. Approaches that allow for the selective targeting of critical populations of cells and particular pathways in the brain have the potential to both avoid side effects and improve efficacy. Chemogenetic methods, which combine the selective expression of designer receptors with designer drugs, have rapidly grown in use in the neurosciences, including in epilepsy. This review will briefly highlight the history of chemogenetics, their applications to date in epilepsy, and the potential (and potential hurdles to overcome) for future translation.
癫痫药物治疗的根本共性在于对神经元兴奋性的调节。这带来了一个明显的挑战——有规律的神经元兴奋对正常功能至关重要,因此扰乱这种活动会导致副作用。此外,尽管经过数十年的药物研发,目前药物治疗的疗效仍不完整。能够选择性靶向大脑中关键细胞群和特定通路的方法,有潜力既能避免副作用又能提高疗效。化学遗传学方法将设计受体的选择性表达与设计药物相结合,在神经科学领域(包括癫痫研究)的应用迅速增加。本综述将简要介绍化学遗传学的历史、其迄今在癫痫中的应用,以及未来转化应用的潜力(和需要克服的潜在障碍)。