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兴奋性氨基酸作为治疗药物:通过解决兴奋性毒性来逆转神经退行性轨迹。

Excitatory amino acids as therapeutic agents: Reversing neurodegenerative trajectory by tackling excitotoxicity.

作者信息

Dhurandhar Yogita, Tomar Shubham, Namdeo Kamta P, Bodakhe Surendra H

机构信息

Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur Chhattisgarh, 495009, India.

National Coordination Centre, Pharmacovigilance Programme of India, Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, Government of India, Sector 23, Rajnagar, Ghaziabad, 201002, Uttar Pradesh, India.

出版信息

Neurol Sci. 2025 Feb;46(2):549-560. doi: 10.1007/s10072-024-07880-3. Epub 2024 Nov 15.

Abstract

Neurodegenerative diseases pose significant challenges to healthcare systems globally due to their complex etiology and relentless progression, often rendering conventional treatments ineffective. Recent advances have spotlighted excitatory amino acids, particularly D-amino acids, once considered as products of metabolism of the microbiota or deriving from food intake. This review explores the role of D-amino acids in mitigating excitotoxicity-a process characterized by excessive calcium influx through aberrant N-methyl-D-aspartate receptor (NMDAR) activation, which is implicated in the pathogenesis of diseases like Alzheimer's disease. By providing alternative pathways for neuronal signaling and protecting against excitotoxic damage, D-amino acids offer a novel approach to reversing neurodegenerative trajectories. Future research should focus on elucidating the detailed mechanisms of action of these compounds, evaluating their therapeutic potential through rigorous preclinical and clinical trials, and developing effective delivery systems to optimize their neuroprotective effects. This emerging field holds promise for developing innovative treatment strategies that could significantly improve outcomes for patients with neurodegenerative disorders.

摘要

神经退行性疾病因其复杂的病因和持续进展,给全球医疗系统带来了重大挑战,常常使传统治疗方法无效。最近的进展突出了兴奋性氨基酸,特别是D-氨基酸,它们曾被认为是微生物群代谢产物或来源于食物摄入。本综述探讨了D-氨基酸在减轻兴奋性毒性中的作用——这一过程的特征是通过异常的N-甲基-D-天冬氨酸受体(NMDAR)激活导致过量钙内流,而这与阿尔茨海默病等疾病的发病机制有关。通过为神经元信号传导提供替代途径并防止兴奋性毒性损伤,D-氨基酸为逆转神经退行性轨迹提供了一种新方法。未来的研究应集中于阐明这些化合物的详细作用机制,通过严格的临床前和临床试验评估其治疗潜力,并开发有效的递送系统以优化其神经保护作用。这一新兴领域有望开发出创新的治疗策略,从而显著改善神经退行性疾病患者的治疗效果。

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