Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, Ghal Kalan, G.T Road, Moga, Punjab, 142001, India.
University Institute of Pharmaceutical Sciences and Research, Baba Farid University of Health Sciences, Faridkot, Punjab, India.
Curr Med Chem. 2024;31(38):6251-6271. doi: 10.2174/0929867331666230913100624.
Parkinson's disease (PD) is a devastating neurodegenerative condition that mostly damages dopaminergic neurons in the substantia nigra and impairs human motor function. Males are more likely than females to have PD. There are two main pathways associated with PD: one involves the misfolding of α-synuclein, which causes neurodegeneration, and the other is the catalytic oxidation of dopamine via MAO-B, which produces hydrogen peroxide that can cause mitochondrial damage. Parkin (PRKN), α- synuclein (SNCA), heat shock protein (HSP), and leucine-rich repeat kinase-2 (LRRK2) are some of the target areas for genetic alterations that cause neurodegeneration in Parkinson's disease (PD). Under the impact of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is also important in Parkinson's disease (PD), inhibition of mitochondrial complex 1 results in enhanced ROS generation in neuronal cells. Natural products are still a superior option in the age of synthetic pharmaceuticals because of their lower toxicity and moderate side effects. A promising treatment for PD has been discovered using betacarboline (also known as "β-carboline") and indole alkaloids. However, there are not many studies done on this particular topic. In the herbs containing β-carbolines and indoles, the secondary metabolites and alkaloids, β-carbolines and indoles, have shown neuroprotective and cognitive-enhancing properties. In this review, we have presented results from 18 years of research on the effects of indole and β-carboline alkaloids against oxidative stress and MAO inhibition, two key targets in PD. In the SAR analysis, the activity has been correlated with their unique structural characteristics. This study will undoubtedly aid researchers in looking for new PD treatment options.
帕金森病(PD)是一种破坏性的神经退行性疾病,主要损害黑质中的多巴胺能神经元,并损害人类的运动功能。男性比女性更容易患 PD。与 PD 相关的主要有两条途径:一条涉及α-突触核蛋白的错误折叠,导致神经退行性变,另一条是通过 MAO-B 催化氧化多巴胺,产生过氧化氢,导致线粒体损伤。Parkin(PRKN)、α-突触核蛋白(SNCA)、热休克蛋白(HSP)和富含亮氨酸重复激酶-2(LRRK2)是导致帕金森病(PD)神经退行性变的遗传改变的一些靶点。在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)的影响下,它在帕金森病(PD)中也很重要,线粒体复合物 1 的抑制导致神经元细胞中 ROS 的产生增加。由于其毒性较低,副作用适中,天然产物在合成药物时代仍然是一个较好的选择。使用β-咔啉(也称为“β-咔啉”)和吲哚生物碱发现了一种治疗 PD 的有前途的方法。然而,关于这个特定主题的研究并不多。在含有β-咔啉和吲哚的草药中,次生代谢物和生物碱β-咔啉和吲哚表现出神经保护和认知增强特性。在本综述中,我们展示了 18 年来对吲哚和β-咔啉生物碱对氧化应激和 MAO 抑制的影响的研究结果,这是 PD 的两个关键靶点。在 SAR 分析中,活性与其独特的结构特征相关联。这项研究无疑将有助于研究人员寻找新的 PD 治疗方法。