Berberine can be a Potential Therapeutic Agent in Treatment of Huntington's Disease: A Proposed Mechanistic Insight.

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Molecular Neurobiology Pub Date : 2025-11-01 Epub Date: 2025-05-16 DOI:10.1007/s12035-025-05054-6
Seema Sharma, Inderpreet Kaur, Naina Dubey, Neelima Goswami, Sampat Singh Tanwar
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引用次数: 0

Abstract

Huntington's disease (HD) is a genetic neurodegenerative disorder caused by CAG repeat expansion in the HTT gene, producing mutant huntingtin (mHTT) protein. This leads to neuronal damage through protein aggregation, transcriptional dysregulation, excitotoxicity, and mitochondrial dysfunction. mHTT impairs protein clearance and alters gene expression, energy metabolism, and synaptic function. Therapeutic strategies include enhancing mHTT degradation, gene silencing via antisense oligonucleotides and RNAi, promoting neuroprotection through BDNF signaling, and modulating neurotransmitters like glutamate and dopamine. Berberine, a natural isoquinoline alkaloid, has emerged as a promising therapeutic option for HD due to its multifaceted neuroprotective properties. Research indicates that berberine can mitigate the progression of neurodegenerative diseases, including HD, by targeting various molecular pathways. It exhibits antioxidant, anti-inflammatory, and autophagy-enhancing effects, which are crucial in reducing neuronal damage and apoptosis associated with HD. These properties make berberine a potential candidate for therapeutic intervention in HD, as demonstrated in both cellular and animal models. Berberine activates the PI3K/Akt pathway, which is vital for cell survival and neuroprotection. It reduces oxidative stress and neuroinflammation, both of which are implicated in HD pathology. Berberine enhances autophagic processes, promoting the degradation of mutant huntingtin protein, a key pathological feature of HD. In transgenic HD mouse models, berberine administration has been shown to alleviate motor dysfunction and prolong survival. It effectively reduces the accumulation of mutant huntingtin in cultured cells, suggesting a direct impact on the disease's molecular underpinnings. Berberine's safety profile, established through its use in treating other conditions, supports its potential for clinical trials in HD patients. Its ability to modulate neurotransmitter levels and engage multiple signaling pathways further underscores its therapeutic promise. While berberine shows significant potential as a therapeutic agent for HD, further research is necessary to fully elucidate its mechanisms and optimize its clinical application. The current evidence in the review paper, primarily from preclinical studies, provides a strong foundation for future investigations into berberine's efficacy and safety in human HD patients.

小檗碱可能是一种潜在的治疗亨廷顿病的药物:一种建议的机制见解。
亨廷顿氏病(HD)是一种遗传性神经退行性疾病,由HTT基因CAG重复扩增引起,产生突变的亨廷顿蛋白(mHTT)。这通过蛋白质聚集、转录失调、兴奋性毒性和线粒体功能障碍导致神经元损伤。mHTT损害蛋白清除,改变基因表达、能量代谢和突触功能。治疗策略包括增强mHTT降解,通过反义寡核苷酸和RNAi进行基因沉默,通过BDNF信号传导促进神经保护,调节谷氨酸和多巴胺等神经递质。小檗碱是一种天然的异喹啉生物碱,由于其多方面的神经保护特性,已成为一种有前途的治疗HD的选择。研究表明,小檗碱可以通过靶向多种分子途径减缓包括HD在内的神经退行性疾病的进展。它具有抗氧化、抗炎和增强自噬的作用,这对于减少HD相关的神经元损伤和凋亡至关重要。这些特性使小檗碱成为HD治疗干预的潜在候选者,这在细胞和动物模型中都得到了证实。小檗碱激活PI3K/Akt通路,这对细胞存活和神经保护至关重要。它可以减少氧化应激和神经炎症,这两者都与HD病理有关。小檗碱增强自噬过程,促进突变亨廷顿蛋白的降解,这是HD的一个关键病理特征。在转基因HD小鼠模型中,黄连素已被证明可以缓解运动功能障碍并延长生存期。它有效地减少了培养细胞中突变亨廷顿蛋白的积累,表明对疾病的分子基础有直接影响。小檗碱的安全性,通过其用于治疗其他疾病,支持其在HD患者的临床试验的潜力。其调节神经递质水平和参与多种信号通路的能力进一步强调了其治疗前景。虽然小檗碱作为一种治疗HD的药物具有很大的潜力,但需要进一步的研究来充分阐明其作用机制并优化其临床应用。目前的证据主要来自临床前研究,为未来研究黄连素对人类HD患者的疗效和安全性提供了坚实的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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