Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
Department of Pharmacology, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh, India.
Curr Protein Pept Sci. 2024;25(7):507-526. doi: 10.2174/0113892037275221240327042353.
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.
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)和肌萎缩侧索硬化症(ALS),是全球面临的重大且日益严峻的健康挑战。目前的治疗方法主要侧重于症状管理,而不是改变疾病进展。在这篇综述中,我们讨论了这些疾病的主要治疗策略,并强调了它们的局限性。对于 AD,主要的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,通常被使用。HD 主要通过对症治疗进行管理,可延长 ALS 患者的生存期。然而,这些治疗方法都无法阻止或显著减缓神经退行性过程。相比之下,本综述强调了生物活性肽作为潜在治疗剂的新兴研究。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,可能调节疾病过程。临床前研究表明,生物活性肽可能减轻氧化应激、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有限,但显示出有希望的初步结果。例如,半缩醛,一种 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,尽管由于副作用其开发被停止。尽管取得了这些进展,但仍存在许多挑战,包括确定最佳的肽、确认其作用机制以及克服其递送到大脑的障碍。未来的研究应优先发现和开发新型生物活性肽,并加深对其药代动力学和药效动力学的理解。最终,这种方法可能会为神经退行性疾病提供更有效的治疗方法,超越症状管理,从而有可能改变这些毁灭性疾病的进程。
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