Wang Ming-Ming, Miao Dan, Cao Xi-Peng, Tan Lin, Tan Lan
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China.
Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China.
Ann Transl Med. 2018 May;6(10):177. doi: 10.21037/atm.2018.04.20.
Alzheimer's disease (AD) is known as the most predominant cause of dementia among the aged people. Previously, two hallmarks of AD pathology including extracellular amyloid-β (Aβ) deposition and neurofibrillary tangles (NFTs) inside neurons have been identified. With a better understanding of this disease, neuroinflammation has been a focus, and as its initial event, innate immune activation plays an indispensable role. In brain, as an endogenous stimulator, extracellular Aβ deposition activates innate immunity through binding to the pattern recognition receptors (PRR), thus leading to the production and release of substantial inflammatory mediators (NO and ROS) and cytokines (IL-1β, IL-10, IL-33 and TNF-α) contributing to the development of AD. Epidemiologic evidence has suggested an affirmative influence of non-steroidal anti-inflammatory drugs (NSAIDs) on delaying the progression of AD. Therefore, blocking the inflammatory process may be an effective way to delay or even cure AD. In this review, we mainly elucidate the mechanism underlying these immune responses in AD pathogenesis and attempt to seek the therapeutic methods targeting neuroinflammation.
阿尔茨海默病（AD）是老年人痴呆症最主要的病因。此前，已确定AD病理学的两个标志，即细胞外β淀粉样蛋白（Aβ）沉积和神经元内神经原纤维缠结（NFTs）。随着对这种疾病的深入了解，神经炎症成为研究焦点，作为其初始事件，先天免疫激活起着不可或缺的作用。在大脑中，作为内源性刺激物，细胞外Aβ沉积通过与模式识别受体（PRR）结合激活先天免疫，从而导致大量炎症介质（NO和ROS）和细胞因子（IL-1β、IL-10、IL-33和TNF-α）的产生和释放，促进AD的发展。流行病学证据表明非甾体抗炎药（NSAIDs）对延缓AD进展有积极影响。因此，阻断炎症过程可能是延缓甚至治愈AD的有效方法。在本综述中，我们主要阐明AD发病机制中这些免疫反应的潜在机制，并试图寻找针对神经炎症的治疗方法。
