Ul Islam Badar, Khan Mohd Shahnawaz, Jabir Nasimudeen R, Kamal Mohammad Amjad, Tabrez Shams
Department of Biochemistry, J. N. Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, India.
Protein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Curr Top Med Chem. 2017;17(12):1400-1407. doi: 10.2174/1568026617666170103163715.
Alzheimer's disease (AD) is an irreversible multifaceted neurodegenerative disorder that gradually degrades neuronal cells. Presently, it is the most common reason for the memory loss and dementia in older individuals. It is patho-physiologically described by extracellular amyloid beta (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) retention, neuronal decline, and neurotransmitter system derangement. Various receptors such as nicotinic acetylcholine, N-methyl-D-aspartate, insulin, serotonin, adenosine, and histamine are actively involved in the physiological progression of AD. Till date memantine and only four other acetylcholinesterase inhibitors have been approved for the treatment of AD by US Food and Drug Administration (US-FDA). Hence, there is a critical need to explore and develop novel and helpful management systems which could specifically target different receptors involved in AD progression. We believe that these receptors targeting will either impede the disease onset or slow down its pathogenesis. In the present review, we tried to uncover some receptors that could be blocked by novel inhibitors and ultimately used for the therapeutic management of AD.
阿尔茨海默病(AD)是一种不可逆的多方面神经退行性疾病,会逐渐使神经元细胞退化。目前,它是老年人记忆力丧失和痴呆的最常见原因。其病理生理学特征为细胞外β淀粉样蛋白(Aβ)沉积、细胞内神经原纤维缠结(NFTs)潴留、神经元衰退和神经递质系统紊乱。多种受体,如烟碱型乙酰胆碱受体、N-甲基-D-天冬氨酸受体、胰岛素受体、5-羟色胺受体、腺苷受体和组胺受体,都积极参与了AD的生理进程。迄今为止,美金刚和仅其他四种乙酰胆碱酯酶抑制剂已被美国食品药品监督管理局(US-FDA)批准用于治疗AD。因此,迫切需要探索和开发新的、有用的管理系统,该系统可以特异性地靶向参与AD进展的不同受体。我们相信,这些针对受体的方法将要么阻止疾病的发作,要么减缓其发病机制。在本综述中,我们试图揭示一些可被新型抑制剂阻断并最终用于AD治疗管理的受体。