ABSTRACT Irreversible peripheral neurodegenerative diseases such as diabetic peripheral neuropathy are becoming increasingly common due to rising rates of diabetes mellitus; however, no effective therapeutic treatments have been developed. One of main causes of irreversible peripheral neurodegenerative diseases is dysfunction in Schwann cells, which are neuroglia unique to the peripheral nervous system (PNS). Because homeostasis of calcium (Ca2+) and magnesium (Mg2+) is essential for Schwann cell dynamics, the regulation of these cations is important for controlling peripheral nerve degeneration and regeneration. Transient receptor potential melastatin 7 (TRPM7) is a non-selective ion (Ca2+ and Mg2+) channel that is expressed in Schwann cells. In the present study, we demonstrated in an ex vivo culture system that inhibition of TRPM7 during peripheral nerve degeneration (Wallerian degeneration) suppressed dedifferentiable or degenerative features (trans-dedifferentiation and proliferation) and conserved a differentiable feature of Schwann cells. Our results indicate that TRPM7 could be very useful as a molecular target for irreversible peripheral neurodegenerative diseases, facilitating discovery of new therapeutic methods for improving human health.

中文翻译：

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抑制瞬时受体电位 melastatin 7 (TRPM7) 在 Wallerian 变性期间防止雪旺细胞转去分化和增殖

摘要 由于糖尿病发病率的上升，不可逆的周围神经退行性疾病如糖尿病周围神经病变变得越来越普遍。然而，尚未开发出有效的治疗方法。不可逆周围神经退行性疾病的主要原因之一是雪旺细胞功能障碍，这是周围神经系统 (PNS) 特有的神经胶质细胞。由于钙 (Ca2+) 和镁 (Mg2+) 的稳态对于雪旺细胞动力学至关重要，因此这些阳离子的调节对于控制周围神经变性和再生很重要。瞬时受体电位 melastatin 7 (TRPM7) 是一种在雪旺细胞中表达的非选择性离子（Ca2+ 和 Mg2+）通道。在目前的研究中，我们在体外培养系统中证明，在外周神经变性（沃勒变性）期间抑制 TRPM7 抑制了去分化或退化特征（反式去分化和增殖），并保留了雪旺细胞的可分化特征。我们的结果表明，TRPM7 作为不可逆转的周围神经退行性疾病的分子靶标可能非常有用，有助于发现改善人类健康的新治疗方法。