Robbins Miranda
MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Ave, Trumpington, Cambridge, UK; University of Cambridge, Department of Zoology, Cambridge, UK.
Neural Regen Res. 2023 Dec;18(12):2633-2637. doi: 10.4103/1673-5374.373670.
Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders (Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating (1) the broad class of chemicals termed "small molecules"; (2) adaptive immunity through both passive and active antibody treatments; (3) innate immunity with an emphasis on microglial modulation; (4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.
实验技术和计算技术的进步持续快速发展，为神经退行性疾病的治疗提供了新途径。尽管如此，在与Tau相关的神经退行性疾病的后期临床试验中，只有少数药物显示出成功的效果。最常用的治疗方法是对症治疗，如胆碱酯酶抑制剂和N-甲基-D-天冬氨酸受体阻滞剂，它们已被批准用于治疗阿尔茨海默病。由于诊断筛查能够在更早的时间点检测出疾病，该领域需要能够预防或显著延缓这些疾病进展的症状前治疗方法（科伊切夫等人，2019年）。这些方法可能与后期治疗不同，后期治疗可能有助于改善症状，并在早期诊断筛查失败且症状变得更严重时减缓疾病进展。本综述将重点介绍学术和工业研究中用于确定治疗与Tau相关的神经退行性疾病的治疗策略的五个关键途径。这些途径包括研究（1）被称为“小分子”的一大类化学物质；（2）通过被动和主动抗体治疗的适应性免疫；（3）以小胶质细胞调节为重点的先天性免疫；（4）认为与Tau相关的神经退行性疾病是突触病变的突触区室。尽管由于阿尔茨海默病的普遍性，本综述将重点关注该疾病，但也将论证针对其他tau蛋白病的必要性，因为通过将阿尔茨海默病理解为一种与Tau相关的神经退行性疾病，我们或许能够推广治疗方案。出于这个原因，每个主题都将补充与Tau蛋白作为直接治疗靶点相关的更多细节。
