Q-Der: a next-generation CoQ10 analogue supercharging neuroprotection by combating oxidative stress and enhancing mitochondrial function.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-02-25 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1525103

Matteo Micucci, Federico Gianfanti, Sabrina Donati Zeppa, Giosuè Annibalini, Barbara Canonico, Fabiana Fanelli, Roberta Saltarelli, Riham Osman, Mariele Montanari, Daniele Lopez, Gemma Nasoni, Giovanna Panza, Erik Bargagni, Francesca Luchetti, Michele Retini, Michele Mari, Giovanni Zappia, Vilberto Stocchi, Alessia Bartolacci, Sabrina Burattini, Michela Battistelli

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引用次数: 0

Abstract

Background: Mitochondrial dysfunction and oxidative stress are central mechanisms in the progression of neurodegenerative diseases. This study first evaluated the toxicity of Q-Der (Q10-diacetate), a derivative of Coenzyme Q10, in HT22 hippocampal neurons under normal and oxidative stress conditions.

Methods: HT22 cells were treated with Q-Der at 2.5, 5 and 10 µM with and without rotenone. Mitochondrial superoxide production (Mitosox), gene expression (via qRT-PCR), and protein levels (via Western blot) were measured. Morphological analyses were performed using transmission (TEM) and scanning (SEM) electron microscopes.

Results: Q-Der significantly reduced mitochondrial superoxide levels, particularly at 5 μM, and upregulated key mitochondrial biogenesis genes, including PGC-1α and TFAM. Additionally, it restored the expression of MT-ND1 and MT-COI, which were downregulated by rotenone. Western blot results showed a significant recovery in CV-ATP5A (complex V) expression (p < 0.05), preserving mitochondrial ATP production. Morphological analyses further confirmed Q-Der's ability to maintain cellular and mitochondrial structure under stress conditions.

Conclusion: These findings suggest that Q-Der is non-toxic under normal conditions and protects against oxidative stress, supporting its potential as a therapeutic agent for neurodegenerative diseases.

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Q-Der：下一代辅酶q10类似物通过对抗氧化应激和增强线粒体功能增强神经保护。

背景：线粒体功能障碍和氧化应激是神经退行性疾病进展的主要机制。本研究首先评估了辅酶Q10的衍生物Q-Der （Q10-diacetate）在正常和氧化应激条件下对HT22海马神经元的毒性。方法：加鱼藤酮和不加鱼藤酮的Q-Der分别在2.5、5和10µM条件下处理HT22细胞。检测线粒体超氧化物生成（Mitosox）、基因表达（通过qRT-PCR）和蛋白水平（通过Western blot）。形态学分析采用透射电镜（TEM）和扫描电镜（SEM）进行。结果：Q-Der显著降低了线粒体超氧化物水平，特别是在5 μM时，并上调了关键的线粒体生物发生基因，包括PGC-1α和TFAM。此外，它还恢复了被鱼藤酮下调的MT-ND1和MT-COI的表达。Western blot结果显示，CV-ATP5A（复合体V）表达显著恢复（p < 0.05），线粒体ATP生成得以保留。形态学分析进一步证实了Q-Der在应激条件下维持细胞和线粒体结构的能力。结论：这些发现表明，Q-Der在正常情况下是无毒的，并且可以抵抗氧化应激，支持其作为神经退行性疾病的治疗药物的潜力。

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

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.