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HDAC6 as a potential therapeutic target for peripheral nerve disorders

机译：HDAC6作为外周神经疾病的潜在治疗靶标

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Introduction: Peripheral neuropathies are a heterogeneous group of diseases that are characterized by a progressive, ascending loss of nerve function arising from the peripheral regions of the limbs. The phenotypic overlap between different types of hereditary and acquired peripheral neuropathies indicates that similar pathophysiological processes are at play. Many downstream pathways in peripheral neurons, such as axonal transport, protein degradation, and interactions with Schwann cells, organelle damage, channelopathies, and neuroinflammatory signaling, have been proposed and each affects peripheral nerves in a negative way. Histone deacetylase 6 (HDAC6) plays an important role at the intersection of these converging pathogenic pathways. The enzymatic deacetylase activity of HDAC6 is upregulated in neurodegenerative disorders and typically results in downstream neuronal stress. Areas covered: The role of HDAC6 in the common pathogenic mechanisms of peripheral neuropathies. In addition, we discuss the current preclinical and clinical HDAC6 inhibitors (HDAC6i), their chemical structure, development, and limitations. Expert opinion: The development and testing of non-hydroxamic acid-based, should be the focus of the future research. Moreover, HDAC6i should be further investigated as a preventative measure and therapeutic strategy for inherited and acquired peripheral neuropathies.
机译：简介：外周神经病是一种异质疾病，其特征在于肢体周围区域引起的渐进性，上升损失的神经功能。不同类型的遗传和获得的外周神经病之间的表型重叠表明相似的病理生理过程在游戏中。已经提出了许多下游途径，例如轴突式，例如轴突转换，蛋白质降解和与施旺细胞的相互作用，有机体损伤，通道病和神经肾性发红信号传导，各自以负面的方式影响外周神经。组蛋白脱乙酰酶6（HDAC6）在这些会聚致病途径的交叉处起重要作用。 HDAC6的酶促脱乙酰酶活性在神经变性紊乱中上调，通常导致下游神经元应力。涵盖的区域：HDAC6在外周神经病的常见致病机制中的作用。此外，我们讨论目前的临床前和临床HDAC6抑制剂（HDAC6i），其化学结构，发展和局限性。专家意见：非羟肟酸的发展和检测应成为未来研究的重点。此外，应进一步研究HDAC6i作为遗传和获得的外周神经病的预防措施和治疗策略。

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