The Role of the Adrenergic System in Neurodegeneration and Oxidative Stress-Induced Damage to the Brain

IF 0.5 4区 医学 Q4 NEUROSCIENCES Neurochemical Journal Pub Date : 2024-01-30 DOI:10.1134/s1819712423040165
A. L. Manukyan, L. S. Hunanyan, L. M. Sukiasyan, W. H. Frey II, K. B. Yenkoyan, L. G. Danielyan, M. M. Melkonyan
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Abstract

Stress is one of the major contributing factors to the development of neurodegenerative diseases and mental disorders. These pathologies are reportedly characterized by progressive loss of neurons and impaired motor and cognitive functions. Changes in stress-induced mechanisms, such as oxidative stress (OS) with corresponding neurotransmitters’ interplay are important for both, the mechanisms of defense and the progression of mental disorders. OS implies an imbalance in the pro-oxidant/antioxidant homeostasis resulting in the generation of aggressive radicals, reactive oxygen species (ROS), and exaggeration of neurodegenerative disease. However, in clinical trials, antioxidants such as alfa-tocopherol have not provided efficacious protection as an alternative therapy for neurodegenerative diseases. Norepinephrine (NE) is the main stress hormone capable of modulating the stress response and providing neuroprotection during neurodegeneration by limiting the production of ROS and stimulating the antioxidative defense, especially against the OH radical. This in turn leads to the protection of cells from ROS-mediated damage and the improvement of cognitive and behavioral functions. Mounting evidence from preclinical studies in the last decade suggests the α2-adrenoblockers-mediated increase of NE release in the brain to be a promising therapeutic approach in neurodegenerative diseases. In this review, we focus on the role of (1) OS in neurodegenerative diseases; (2) the role of adrenergic receptors (ARs) in disease pathology and mechanisms of defense during neurodegeneration, and (3) the adrenergic signaling system in cognitive functions and neuroprotection provided by NE and α2-adrenoblockers.

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肾上腺素能系统在神经变性和氧化应激引起的脑损伤中的作用
摘要压力是导致神经退行性疾病和精神障碍的主要因素之一。据报道,这些病症的特点是神经元逐渐丧失,运动和认知功能受损。应激诱导机制的变化,如氧化应激(OS)与相应神经递质的相互作用,对精神障碍的防御机制和发展都很重要。氧化应激意味着促氧化剂/抗氧化剂平衡失调,从而产生攻击性自由基、活性氧(ROS),加剧神经退行性疾病。然而,在临床试验中,α-生育酚等抗氧化剂作为神经退行性疾病的替代疗法并未提供有效的保护。去甲肾上腺素(NE)是一种主要的应激激素,能够调节应激反应,并在神经变性过程中通过限制 ROS 的产生和刺激抗氧化防御(尤其是针对 OH 自由基)来提供神经保护。这反过来又能保护细胞免受 ROS 介导的损伤,改善认知和行为功能。近十年来临床前研究中越来越多的证据表明,α2-肾上腺素受体阻滞剂介导的脑内NE释放增加是治疗神经退行性疾病的一种很有前景的方法。在这篇综述中,我们将重点讨论:(1) OS 在神经退行性疾病中的作用;(2) 肾上腺素能受体(AR)在疾病病理和神经退行性疾病防御机制中的作用;(3) 肾上腺素能信号系统在认知功能中的作用以及 NE 和 α2-肾上腺受体阻滞剂提供的神经保护。
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来源期刊
Neurochemical Journal
Neurochemical Journal 医学-神经科学
自引率
20.00%
发文量
40
审稿时长
>12 weeks
期刊介绍: Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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