6-羟多巴胺诱导的斑马鱼帕金森病中天然神经保护化合物的应用现状及展望

IF 2.7 4区 医学 Q3 NEUROSCIENCES CNS & neurological disorders drug targets Pub Date : 2023-01-01 DOI:10.2174/1871527322666221028152600
Sara Abidar, Lucian Hritcu, Mohamed Nhiri
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引用次数: 1

摘要

背景与目的:帕金森病(PD)是一种神经退行性疾病,其特征是黑质致密部多巴胺能神经元变性,导致纹状体多巴胺丢失,从而导致PD的经典运动症状:静息性震颤、强直、运动迟缓/运动障碍。此外,左旋多巴的疗效随着长期使用而下降,产生严重的运动并发症。神经保护意味着使用不同的神经保护策略来防止脑退化和神经元丢失。本文对6-羟多巴胺(6-OHDA)诱导斑马鱼帕金森病的天然神经保护化合物进行综述和分析。结果:目前的研究收集了23种不同的天然物质,分为5个不同的类别,即草药提取物、草药配方、生物活性化合物、海洋产品和海洋提取物。它们调节PD发病机制中涉及的各种信号通路,并表现出特定的活性,如抗焦虑谱,改善运动障碍,恢复记忆障碍,防止DNA丢失,抑制乙酰胆碱酯酶,减少脂质过氧化和抗炎活性,增强脑抗氧化酶。结论与展望:本文综述了最有前途的天然神经保护化合物,这些化合物对斑马鱼模型中6-羟多巴胺引起的损伤的潜在疗效进行了评估。这些天然物质值得进一步研究,以确定它们的最佳浓度、生物利用度以及它们通过血脑屏障对PD发挥作用的能力。此外,还需要对PD的分子机制有完整的了解,并进行更大规模的人类流行病学和随机临床试验。
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The Natural Neuroprotective Compounds Used in the 6-Hydroxydopamine- Induced Parkinson's Disease in Zebrafish: The Current Applications and Perspectives.

Background and objective: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta, resulting in the loss of dopamine in the striatum, leading thus to the PD classic movement symptoms: resting tremor, rigidity, and bradykinesia/akinesia. Furthermore, Levodopa's efficacy declines with long-term use, generating serious motor complications. Neuroprotection implies the use of different agents exhibiting various neuroprotective strategies to prevent brain degeneration and neuron loss. The present review aims to summarize and analyze the natural neuroprotective compounds that have been tested against PD induced by the 6-hydroxydopamine (6-OHDA) in zebrafish.

Results: The current study collected 23 different natural substances, divided into five distinct categories, namely herbal extracts, herbal formulations, bioactive compounds, marine products, and marine extracts. They modulate various signaling pathways involved in PD pathogenesis and exhibit specific activities such as an anxiolytic profile, improving locomotor impairment, restoring memory troubles, preventing DNA loss, inhibiting acetylcholinesterase, reducing lipid peroxidation and antiinflammatory activity, and enhancing the brain antioxidant enzymes.

Conclusion and perspectives: This review discusses the most promising natural neuroprotective compounds that have been evaluated for their potential efficiency on the 6-OHDA-induced lesions in the zebrafish model. These natural substances deserve further consideration for determination of their optimum concentrations, bioavailability, and their ability to cross the blood-brain-barrier to exert their effects on PD. Furthermore, a complete understanding of the molecular mechanisms involved in PD and larger epidemiologic and randomized clinical trials in humans is also required.

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来源期刊
CiteScore
5.10
自引率
3.30%
发文量
158
审稿时长
6-12 weeks
期刊介绍: Aims & Scope CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. CNS & Neurological Disorders - Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
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