Charnoly小体作为细胞损伤的通用生物标志物

Sushil Sharma , Manuchair Ebadi
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引用次数: 5

摘要

Charnoly小体(CB)是一种多形性的、电子密集的、多层的、凋亡前的、线粒体细胞损伤的生物标志物。由于线粒体生物能量受损,营养应激和环境毒素诱导高度脆弱的发育中的神经元形成CB;然而,营养康复、生理性补锌和金属硫蛋白(MTs)可抑制CB的形成。在轴突丘交界处积累的CBs可能会损害突触末端离子、神经递质、嗜神经因子和酶的轴浆运输。因此,可以开发药物来抑制神经退行性疾病和心血管疾病中CB的形成。此外,在癌症化疗中非特异性诱导超增殖细胞形成CB会导致脱发、骨髓抑制、胃肠道症状、心血管毒性和不孕症。因此,可以开发药物来诱导癌症干细胞特异性CB形成,以治疗耐多药恶性肿瘤和慢性感染。线粒体DNA的天然丰度和遗传易感性使CB成为具有临床意义的早期、独特和敏感的通用生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Charnoly body as a universal biomarker of cell injury

The Charnoly body (CB) is a pleomorphic, electron-dense, multilamellar, preapoptotic, mitochondrial biomarker of cell injury. Nutritional stress and environmental toxins induce CB formation in highly vulnerable developing neurons because of compromised mitochondrial bioenergetics; however, nutritional rehabilitation, physiological zinc supplementation, and metallothioneins (MTs) inhibit CB formation. Accumulation of CBs at the junction of the axon hillock may impair the axoplasmic transport of ions, neurotransmitters, neurotropic factors, and enzymes at the synaptic terminals. Therefore, drugs may be developed to inhibit CB formation in neurodegenerative and cardiovascular diseases. In addition, nonspecific induction of CB formation in hyperproliferating cells with cancer chemotherapy causes as adverse effects alopecia, myelosuppression, gastrointestinal tract symptoms, cardiovascular toxicity, and infertility. Hence, drugs may be developed to induce cancer stem cell-specific CB formation to cure multidrug-resistant malignancies and chronic infections. Natural abundance and genetic susceptibility of mitochondrial DNA qualify CB as an early, unique, and sensitive universal biomarker of clinical significance.

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