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褪黑素对神经退行性疾病和神经精神疾病中神经回路的调节作用。

Modulation of neural circuits by melatonin in neurodegenerative and neuropsychiatric disorders.

作者信息

Giri Aditi, Mehan Sidharth, Khan Zuber, Das Gupta Ghanshyam, Narula Acharan S, Kalfin Reni

机构信息

Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy Moga, Punjab, India.

IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun;397(6):3867-3895. doi: 10.1007/s00210-023-02939-y. Epub 2024 Jan 16.

Abstract

Neurodegenerative and neuropsychiatric disorders are two broad categories of neurological disorders characterized by progressive impairments in movement and cognitive functions within the central and peripheral nervous systems, and have emerged as a significant cause of mortality. Oxidative stress, neuroinflammation, and neurotransmitter imbalances are recognized as prominent pathogenic factors contributing to cognitive deficits and neurobehavioral anomalies. Consequently, preventing neurodegenerative and neuropsychiatric diseases has surfaced as a pivotal challenge in contemporary public health. This review explores the investigation of neurodegenerative and neuropsychiatric disorders using both synthetic and natural bioactive compounds. A central focus lies on melatonin, a neuroregulatory hormone secreted by the pineal gland in response to light-dark cycles. Melatonin, an amphiphilic molecule, assumes multifaceted roles, including scavenging free radicals, modulating energy metabolism, and synchronizing circadian rhythms. Noteworthy for its robust antioxidant and antiapoptotic properties, melatonin exhibits diverse neuroprotective effects. The inherent attributes of melatonin position it as a potential key player in the pathophysiology of neurological disorders. Preclinical and clinical studies have demonstrated melatonin's efficacy in alleviating neuropathological symptoms across neurodegenerative and neuropsychiatric conditions (depression, schizophrenia, bipolar disorder, and autism spectrum disorder). The documented neuroprotective prowess of melatonin introduces novel therapeutic avenues for addressing neurodegenerative and psychiatric disorders. This comprehensive review encompasses many of melatonin's applications in treating diverse brain disorders. Despite the strides made, realizing melatonin's full neuroprotective potential necessitates further rigorous clinical investigations. By unravelling the extended neuroprotective benefits of melatonin, future studies promise to deepen our understanding and augment the therapeutic implications against neurological deficits.

摘要

神经退行性疾病和神经精神疾病是两大类神经系统疾病,其特征是中枢和外周神经系统的运动和认知功能逐渐受损,并已成为一个重要的死亡原因。氧化应激、神经炎症和神经递质失衡被认为是导致认知缺陷和神经行为异常的主要致病因素。因此,预防神经退行性疾病和神经精神疾病已成为当代公共卫生领域的一项关键挑战。本综述探讨了使用合成和天然生物活性化合物对神经退行性疾病和神经精神疾病的研究。核心关注点是褪黑素,一种由松果体分泌的神经调节激素,它会根据昼夜节律周期进行分泌。褪黑素是一种两亲性分子,具有多方面的作用,包括清除自由基、调节能量代谢和同步昼夜节律。褪黑素以其强大的抗氧化和抗凋亡特性而闻名,具有多种神经保护作用。褪黑素的固有特性使其成为神经疾病病理生理学中一个潜在的关键因素。临床前和临床研究已经证明褪黑素在减轻神经退行性疾病和神经精神疾病(抑郁症、精神分裂症、双相情感障碍和自闭症谱系障碍)的神经病理症状方面具有疗效。褪黑素已被证明的神经保护能力为治疗神经退行性疾病和精神疾病引入了新的治疗途径。这篇全面的综述涵盖了褪黑素在治疗各种脑部疾病中的许多应用。尽管已经取得了进展,但要实现褪黑素的全部神经保护潜力仍需要进一步严格的临床研究。通过揭示褪黑素更广泛的神经保护益处,未来的研究有望加深我们的理解,并增强针对神经缺陷的治疗意义。

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