Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development , HKUST Shenzhen Research Institute , Shenzhen , Guangdong , China.
ACS Chem Neurosci. 2019 Feb 20;10(2):872-879. doi: 10.1021/acschemneuro.8b00402. Epub 2018 Sep 17.
Alzheimer's disease is a progressive neurodegenerative disease, and its incidence is expected to increase owing to the aging population worldwide. Current therapies merely provide symptomatic relief. Therefore, interventions for AD that delay the disease onset or progression are urgently required. Recent genomics and functional studies suggest that immune/inflammatory pathways are involved in the pathogenesis of AD. Although many anti-inflammatory drug candidates have undergone clinical trials, most have failed. This might be because of our limited understanding of the pathological mechanisms of neuroinflammation in AD. However, recent advances in the understanding of immune/inflammatory pathways in AD and their regulatory mechanisms could open up new avenues for drug development targeting neuroinflammation. In this Review, we discuss the mechanisms and status of different anti-inflammatory drug candidates for AD that have undergone or are undergoing clinical trials and explore new opportunities for targeting neuroinflammation in AD drug development.
阿尔茨海默病是一种进行性神经退行性疾病，由于全球人口老龄化，其发病率预计将会增加。目前的治疗方法仅仅提供症状缓解。因此，迫切需要针对 AD 的干预措施，以延缓疾病的发作或进展。最近的基因组学和功能研究表明，免疫/炎症途径参与了 AD 的发病机制。尽管许多抗炎药物候选物已经进行了临床试验，但大多数都失败了。这可能是因为我们对 AD 中神经炎症的病理机制的了解有限。然而，最近对 AD 中免疫/炎症途径及其调节机制的理解的进展，可能为针对神经炎症的药物开发开辟新途径。在这篇综述中，我们讨论了已经或正在进行临床试验的针对 AD 的不同抗炎药物候选物的机制和现状，并探讨了 AD 药物开发中靶向神经炎症的新机会。
