Abstract：
Neurodegenerative disorders, which include Alzheimer\'s disease (AD), Parkinson\'s disease (PD), Huntington\'s disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.
摘要：
神经退行性疾病，其中包括阿尔茨海默病（AD），帕金森病（PD），亨廷顿病（HD），和肌萎缩侧索硬化症（ALS），代表了一个重大和日益增长的全球卫生挑战。目前的治疗主要集中在症状管理，而不是改变疾病进展。在这次审查中,我们讨论了这些疾病的主要治疗策略，强调其局限性。对于AD，主要治疗方法是胆碱酯酶抑制剂和N-甲基-D-天冬氨酸(NMDA)受体拮抗剂.对于PD，多巴胺替代疗法，包括左旋多巴,是常用的。HD主要通过对症治疗来管理，和可重复使用的延长生存在ALS。然而,这些疗法都不能阻止或显著减缓神经变性过程。相比之下,这篇综述重点介绍了生物活性肽作为潜在治疗药物的新兴研究。这些天然存在或合成设计的分子可以与特定的细胞靶标相互作用，潜在的调节疾病过程。临床前研究表明，生物活性肽可以减轻氧化应激，炎症,和蛋白质错误折叠，这是神经退行性疾病的常见病理特征。使用生物活性肽进行神经变性的临床试验有限，但显示了有希望的初步结果。例如,半缩醛,γ-分泌酶抑制剂肽，通过减少淀粉样蛋白β的产生显示出在AD中的潜力，尽管由于副作用而停止了开发。尽管取得了这些进步,许多挑战依然存在,包括确定最佳的肽，确认他们的行动机制，并克服与它们传递到大脑有关的障碍。未来的研究应优先发现和开发新的生物活性肽，并提高我们对其药代动力学和药效学的理解。最终,这种方法可能会导致更有效的治疗神经退行性疾病，超越症状管理，有可能改变这些毁灭性疾病的进程。
