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帕金森病治疗中异常神经递质的恢复与靶向作用

Restoration and targeting of aberrant neurotransmitters in Parkinson's disease therapeutics.

作者信息

Yadav Divya, Kumar Pravir

机构信息

Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi, India; Delhi Technological University (Formerly Delhi College of Engineering), Delhi, 110042, India.

Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi, India; Delhi Technological University (Formerly Delhi College of Engineering), Delhi, 110042, India.

出版信息

Neurochem Int. 2022 Jun;156:105327. doi: 10.1016/j.neuint.2022.105327. Epub 2022 Mar 21.

Abstract

Neurotransmitters are considered as a fundamental regulator in the process of neuronal growth, differentiation and survival. Parkinson's Disease (PD) occurs due to extensive damage of dopamine-producing neurons; this causes dopamine deficits in the midbrain, followed by the alternation of various other neurotransmitters (glutamate, GABA, serotonin, etc.). It has been observed that fluctuation of neurotransmission in the basal ganglia exhibits a great impact on the pathophysiology of PD. Dopamine replacement therapy, such as the use of L-DOPA, can increase the dopamine level, but it majorly ameliorates the motor symptoms and is also associated with long-term complications (for e.g., LID). While the non-dopaminergic system can efficiently target non-motor symptoms, for instance, the noradrenergic system regulates the synthesis of BDNF via the MAPK pathway, which is important in learning and memory. Herein, we briefly discuss the role of different neurotransmitters, implementation of neurotransmitter receptors in PD. We also illustrate the recent advances of neurotransmitter-based drugs, which are currently under in vivo and clinical studies. Reinstating normal neurotransmitter levels has been believed to be advantageous in the treatment of PD. Thus, there is an increasing demand for drugs that can specifically target the neurotransmission system and reinstate the normal levels of neurotransmitters, which might prevent or delay neurodegeneration in PD.

摘要

神经递质被认为是神经元生长、分化和存活过程中的一种基本调节因子。帕金森病(PD)是由于产生多巴胺的神经元广泛受损而发生的;这会导致中脑多巴胺缺乏,随后其他各种神经递质(谷氨酸、γ-氨基丁酸、血清素等)也会发生改变。据观察,基底神经节神经传递的波动对PD的病理生理学有很大影响。多巴胺替代疗法,如使用左旋多巴,可以提高多巴胺水平,但它主要改善运动症状,并且还与长期并发症(例如,异动症)有关。虽然非多巴胺能系统可以有效地针对非运动症状,例如,去甲肾上腺素能系统通过MAPK途径调节脑源性神经营养因子(BDNF)的合成,这在学习和记忆中很重要。在此,我们简要讨论不同神经递质的作用、神经递质受体在PD中的应用。我们还阐述了目前正在进行体内和临床研究的基于神经递质的药物的最新进展。恢复正常的神经递质水平被认为对PD的治疗是有利的。因此,对能够特异性靶向神经传递系统并恢复神经递质正常水平的药物的需求日益增加,这可能预防或延缓PD中的神经退行性变。

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