Department of Pharmacology, I.S.F College of Pharmacy, Ghal Kalan, Moga, Punjab, India.
Department of Pharmacology, I.S.F College of Pharmacy, Ghal Kalan, Moga, Punjab, India; School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences & Technology, Baddi, Solan, H.P., India.
Neuropharmacology. 2018 Jul 1;136(Pt B):271-279. doi: 10.1016/j.neuropharm.2017.11.015. Epub 2017 Nov 10.
Epilepsy is one of the most prevalent neurological disorder affecting more than 50 million people worldwide. Numerous studies have suggested that an imbalance in glutamatergic (excitatory) and GABAergic (inhibitory) neurotransmitter system is one of the dominating pathophysiological mechanisms underlying the occurrence and progression of seizures. Further, this alteration in GABAergic and glutamatergic system disrupts the delicate balance of other neurotransmitters system in the brain. Emerging strides have documented the protective role of GLP-1 signaling on altered neurotransmitters signaling in Epilepsy and associated co-morbidities. GLP-1 is neuropeptide and synthesized by preproglucagon (PPG) neurons in the brain. GLP-1 receptors are widely distributed throughout the brain including hippocampus (CA3 and CA1 region) and implicated in various neurological disorders like Epilepsy. A complete understanding of alteration in neurotransmitters signaling will provide essential insight into the basic pathogenic mechanisms of epilepsy and may uncover novel targets for future drug therapies. Presently, treatment of epilepsy is palliative in nature, providing only symptomatic relief to patients. The apparent or traditional approach of treating epileptic subjects with anti-epileptic drugs is associated with variety of adverse effects. Therefore, alternative approaches that can restore altered neurotransmitter signaling are being tried and adopted. Present review is an attempt to highlight the emerging protective role of GLP-1 signaling on altered neurotransmitters signaling in epilepsy. Authors have made significant efforts to discuss effect of various GLP-1 analogs on various neurotransmitters system and associated molecular and cellular pathways as a potential drug target for the management of epilepsy and associated co-morbidities. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'
癫痫是影响全球超过 5000 万人的最常见神经系统疾病之一。许多研究表明,谷氨酸能(兴奋)和 GABA 能(抑制)神经递质系统的失衡是癫痫发生和发展的主要病理生理机制之一。此外,这种 GABA 能和谷氨酸能系统的改变破坏了大脑中其他神经递质系统的微妙平衡。新兴的研究成果记录了 GLP-1 信号对癫痫和相关合并症中改变的神经递质信号的保护作用。GLP-1 是一种神经肽,由脑内的前胰高血糖素原(PPG)神经元合成。GLP-1 受体广泛分布于大脑,包括海马体(CA3 和 CA1 区),并与癫痫等各种神经疾病有关。对神经递质信号改变的全面了解将为癫痫的基本发病机制提供重要的见解,并可能为未来的药物治疗揭示新的靶点。目前,癫痫的治疗是姑息性的,只能为患者提供症状缓解。用抗癫痫药物治疗癫痫患者的传统方法存在多种不良反应。因此,正在尝试和采用可以恢复改变的神经递质信号的替代方法。本综述试图强调 GLP-1 信号对癫痫中改变的神经递质信号的新兴保护作用。作者做出了巨大努力,讨论了各种 GLP-1 类似物对各种神经递质系统的影响及其相关的分子和细胞途径,作为管理癫痫和相关合并症的潜在药物靶点。本文是题为“代谢损伤作为神经退行性疾病的风险因素”的特刊的一部分。