Exploring novel experimental treatments for major neurodegenerative disorders.
Exploring novel experimental treatments for major neurodegenerative disorders.
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DOI：
10.1002/nep3.31
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发表时间：
2023-12
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急性和慢性神经退行性疾病，如缺血性中风或阿尔茨海默病(AD)，给患者、他们的亲属、照顾者和一般的卫生保健系统带来了主要负担。由于全球人口老龄化以及久坐不动的生活方式和不适当的饮食习惯日益普遍，神经退行性疾病的社会经济影响预计将升级。相反，为神经退行性疾病提供病因治疗的治疗选择很少，有效地减轻了其后果，提高了患者的生活质量。可用的为数不多的治疗选择往往受到时间限制的限制。例如，治疗缺血性中风的再通方法的治疗时间窗口很窄，使大多数患者无法获得。因此，目前的工作集中于改善急性卒中的治疗，包括辅助神经保护或免疫调节干预，以使更多的患者从再通中受益。1类似地，最近使用单抗在AD中靶向淀粉样蛋白β(Aβ)斑块的方法仅在疾病的早期阶段有效。然而，总体的治疗影响仍然不大，伴随着严重副作用的可能性。2因此，迫切需要新的治疗方法。这一期的神经保护以神经退行性疾病的实验性治疗研究的一些令人兴奋的更新为特色，并补充了对以前、当前和未来方法的荟萃分析和回顾。这篇社论将总结和突出这些贡献中提出的最重要的方面。刘等人。建议通过AD神经保护研究倡议(ADNRI)制定一个协调一致的全球战略来对抗AD。在他们对当前AD治疗机会的全面评估中，他们强调了在细胞和系统水平上的神经成像方法对于临床疾病监测和翻译活动的重要性。他们还讨论了AD神经保护干预的当前和潜在的未来方法，提供了神经营养因子和抗炎治疗的详细概述。他们进一步强调了星形胶质细胞和少突胶质细胞在AD中的作用。它们最终集中在AD的代谢、血管和脑膜方面，以及潜在的外周干预和生活方式的改变，从而提供了治疗机会的整体图景。田口等人的工作。与刘和同事提供的见解相互联系。抗Aβ免疫疗法的温和影响间接表明，Aβ可能不是AD的全部发病机制，因此，可能不是唯一的治疗靶点。作者主张探索潜在的靶点，如海马神经发生，以此作为可行的途径。他们的理论基础是AD患者的海马神经发生明显减少。4田口等人。不仅为他们的建议提供了详细的理由，还强调了联合治疗的必要性，以对抗复杂的AD病理。他们还声称
Acute and chronic neurodegenerative disorders such as ischemic stroke or Alzheimer's disease (AD) impose a major burden on patients, their relatives, caregivers, and health care systems in general. The socioeconomic impact of neurodegenerative disorders is anticipated to escalate due to a globally ageing population and the increasing prevalence of sedentary lifestyle and inappropriate dietary habits. On the contrary, there is a paucity of therapeutic options providing causative treatment for neurodegenerative disorders, effectively mitigating their consequences and enhancing patients' quality of life. The few therapeutic options being available are often limited by temporal restrictions. For instance, recanalization approaches for ischemic stroke have a narrow therapeutic time window, rendering them inaccesible for the majority of patients. Current work therefore focuses on improving acute stroke management including adjuvant neuroprotective or immunomodulative interventions to allow more patients to benefit from recanalization. 1 Similarly, recent approaches to target amyloid β (Aβ) plaques using monoclonal antibodies in AD are only effective in the early stages of the disease. However, the overall therapeutic impact remains modest, accompanied by the potential of severe side effects. 2 Hence, there is a pressing need for novel therapeutic approaches. This issue of Neuroprotection features some exciting updates on experimental therapeutic research for neurodegenerative diseases, complemented by meta‐analyses and reviews of previous, current, and future approaches. This editorial will summarize and highlight the most important aspects presented within these contributions. Liu et al. suggest an orchestrated, global strategy to combat AD, through the AD Neuroprotection Research Initiative (ADNRI). In their comprehensive assessment of current therapeutic opportunities for AD, they stress the importance of neuroimaging approaches at both cellular and system levels for clinical disease monitoring and translational activities. They also discuss current as well as potential future approaches for neuroprotective interventions in AD, providing a detailed overview of neurotrophic factors and anti‐inflammatory treatments. They further highlight the role of astrocytes and oligodendrocytes in AD. They finally focus on metabolic, vascular, and meningeal aspects of AD, as well as potential peripheral interventions and lifestyle changes, thus offering a holistic picture of therapeutic opportunities. The work by Taguchi et al. interconnects with the insights offered by Liu and colleagues. The modest impact of anti‐Aβ immunotherapies3 indirectly suggests that Aβ may not singularily constitute the entire pathomechanism in AD and consequently, may not be the only therapeutic target. The authors advocate for exploring potential targets such as the hippocampal neurogenesis as a viable avenue. Their rationale is based on the noteable decline in hippocampal neurogenesis among AD patients. 4 Taguchi et al. not only provide a detailed rationale for their suggestion but also highlight the need for combination treatments to counter the complex AD pathology. They also claim