A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-01-01 DOI:10.2174/0113892037275221240327042353
Kuldeep Singh, Jeetendra Kumar Gupta, Shivendra Kumar, Urvashi Soni
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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.

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常见神经退行性疾病综述:当前的治疗方法和生物活性肽的潜在作用。
神经退行性疾病包括阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)和肌萎缩性脊髓侧索硬化症(ALS),是一项日益严峻的全球性健康挑战。目前的疗法主要侧重于症状控制,而不是改变疾病的进展。在这篇综述中,我们将讨论这些疾病的主要治疗策略,并强调其局限性。对于注意力缺失症,主要治疗手段是胆碱酯酶抑制剂和N-甲基-D-天冬氨酸(NMDA)受体拮抗剂。对于帕金森病,常用的是多巴胺替代疗法,包括左旋多巴。HD 主要采用对症治疗,可重复使用的疗法可延长 ALS 患者的生存期。然而,这些疗法都不能阻止或大大减缓神经退行性过程。与此相反,本综述重点介绍作为潜在治疗药物的生物活性肽的新兴研究。这些天然存在或人工合成的分子可与特定的细胞靶点相互作用,潜在地调节疾病进程。临床前研究表明,生物活性肽可减轻氧化应激、炎症和蛋白质错误折叠,这些都是神经退行性疾病的常见病理特征。使用生物活性肽治疗神经退行性疾病的临床试验还很有限,但初步结果很有希望。例如,γ-分泌酶抑制剂肽半乙缩醛通过减少淀粉样蛋白-β的产生,显示出治疗注意力缺失症的潜力,但由于副作用,其开发工作已经中止。尽管取得了这些进展,但仍存在许多挑战,包括确定最佳多肽、确认其作用机制以及克服与将其输送到大脑有关的障碍。未来的研究应优先考虑新型生物活性肽的发现和开发,并提高我们对其药代动力学和药效学的认识。最终,这种方法可能会为神经退行性疾病带来更有效的疗法,超越症状管理的范畴,有可能改变这些毁灭性疾病的病程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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