Ahmad Khurshid, Khan Saif, Adil Mohd, Saeed Mohd, Srivastava Ashwini Kumar
Department of Biosciences, Integral University, Lucknow.
College of Applied Medical Sciences, University of Ha׳il, Kingdom of Saudi Arabia.
Bioinformation. 2014 Apr 23;10(4):191-5. doi: 10.6026/97320630010191. eCollection 2014.
Neurodegenerative disorders are often associated with excessive neuronal apoptosis. It is well known that apoptosis is regulated by some intracellular proteases, such as, Caspases (cysteine-dependent, aspartate-specific proteases). In fact, Caspase-8 which is an initiator caspase, has been identified as a key mediator of neuronal apoptosis. In addition, Caspase-8 is found to be coupled with the regulation of various neurodegenerative disorders including Alzheimer׳s disease (AD), Parkinson׳s disease (PD), Huntington׳s Diseases (HD) and Dentatorubral Pallidoluysian Atrophy (DRPLA). Caspase-8 inhibition may provide an effective means of treatment for multiple neurodegenerative disorders. Therefore, the present study describes the molecular interaction of some selected natural compounds with known anti neurodegenerative properties with Caspase-8. Docking between Caspase-8 and each of these compounds (separately) was performed using 'Autodock4.2'. Out of all the selected compounds, rosmarinic acid and curcumin proved to be the most potent inhibitors of Caspase-8 with binding energy (ΔG) of -7.10 Kcal/mol and -7.08 Kcal/mol, respectively. However, further in vitro and in vivo studies are needed to validate the anti-neurodegenerative potential of these compounds.
神经退行性疾病通常与神经元过度凋亡有关。众所周知，细胞凋亡受一些细胞内蛋白酶调节，比如半胱天冬酶（天冬氨酸特异性半胱氨酸蛋白酶）。事实上，作为起始半胱天冬酶的半胱天冬酶 -8已被确定为神经元凋亡的关键介质。此外，发现半胱天冬酶 -8与包括阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）和齿状核红核苍白球萎缩症（DRPLA）在内的各种神经退行性疾病的调节有关。抑制半胱天冬酶 -8可能为多种神经退行性疾病提供一种有效的治疗手段。因此，本研究描述了一些具有已知抗神经退行性特性的天然化合物与半胱天冬酶 -8之间的分子相互作用。使用“Autodock4.2”对半胱天冬酶 -8与这些化合物中的每一种（分别）进行对接。在所有选定的化合物中，迷迭香酸和姜黄素被证明是半胱天冬酶 -8最有效的抑制剂，结合能（ΔG）分别为 -7.10千卡/摩尔和 -7.08千卡/摩尔。然而，需要进一步的体外和体内研究来验证这些化合物的抗神经退行性潜力。
