Islam Badar Ul, Tabrez Shams
Department of Biochemistry, J. N. Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, India.
King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia.
Int J Biol Macromol. 2017 Apr;97:700-709. doi: 10.1016/j.ijbiomac.2017.01.076. Epub 2017 Jan 19.
Alzheimer's disease (AD) is a well-known cause of memory loss and dementia in elderly people all across the world. It is pathophysiologically characterized by the extracellular deposition of amyloid beta (Aβ) proteins and retention of intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau proteins. Several enzymes, such as lipoxygenases, acetylcholinesterases, secretases, glycogen synthase kinase 3, caspases, sirtuins have been reported to actively participate in the pathogenesis of AD. Due to the limited drug for the management of AD till now (only memantine and four other acetylcholinesterase inhibitors), there is an urgent need to find out the novel inhibitors that could specifically act against these enzymes or therapeutically important targets, and barricade or decelerate AD progression. In this current review, we aim to unravel various enzymes and their potential inhibitors that could be exploited against AD pathogenesis. We have also covered several other important miscellaneous targets which could be used as AD therapeutics.
阿尔茨海默病（AD）是全球老年人记忆丧失和痴呆的一个众所周知的病因。其病理生理特征是细胞外β淀粉样蛋白（Aβ）沉积和细胞内过度磷酸化tau蛋白神经原纤维缠结（NFTs）的留存。据报道，几种酶，如脂氧合酶、乙酰胆碱酯酶、分泌酶、糖原合酶激酶3、半胱天冬酶、沉默调节蛋白，都积极参与AD的发病机制。由于目前用于治疗AD的药物有限（只有美金刚和其他四种乙酰胆碱酯酶抑制剂），迫切需要找到能够特异性作用于这些酶或治疗重要靶点的新型抑制剂，以阻断或减缓AD的进展。在本综述中，我们旨在揭示各种可用于对抗AD发病机制的酶及其潜在抑制剂。我们还涵盖了其他几个可作为AD治疗药物的重要杂项靶点。
