自组装支架在表观遗传学上重新激活和电化学引导神经元再生，以恢复中枢神经回路
Self-assembling scaffolds epigenetically reactivate and electroactively guide neuronal regeneration to restore central neural circuits.
摘要(中文译文)
中枢神经系统（CNS）损伤是全球范围内导致死亡和长期残疾的主要原因。神经功能缺损反映了中枢神经环路的破坏。环路修复的一个主要障碍是成年CNS神经元内在的低再生潜能——部分与损伤诱导的IIa类组蛋白去乙酰化酶（尤其是HDAC5）核输出失败有关——以及损伤后不利的微环境。在此，我们提出了一种多功能纳米系统，该体系包载IIa类HDAC4/5选择性抑制剂LMK-235，并具有电活性聚苯胺涂层，其上不对称分布着5-羟色胺基团。到达损伤部位后，我们的纳米系统组装成大孔支架，从而（i）抑制神经元中核滞留的IIa类HDAC的活性，进而重新激活内在再生程序，（ii）调节小胶质细胞活化以减轻神经炎症，（iii）提供电活性界面促进活动依赖性突触重连。这种多管齐下的策略展示了一个具有转化潜力的集成平台，可用于环路断开限制恢复的CNS疾病。
Abstract
Central nervous system (CNS) injury is a leading cause of death and long-term disability worldwide. Neurological deficits reflect disruption of central neural circuits. A major barrier to circuit repair is the intrinsically low regenerative potential of adult CNS neurons-linked in part to failure of injury-induced nuclear export of class IIa histone deacetylases (notably HDAC5)-together with a hostile post-injury microenvironment. Here we present a multifunctional nanosystem, encapsulating the class IIa HDAC4/5-selective inhibitor LMK-235 and featuring an electroactive polyaniline coating with asymmetrically distributed 5-hydroxytryptamine moieties. Upon reaching the lesion, our nanosystem assembles into large-pore scaffolds that (i) inhibit the activity of nuclear-retained class IIa HDACs in neurons and thereby reactivate intrinsic regenerative programs, (ii) regulate microglial activation to mitigate neuroinflammation, and (iii) provide an electroactive interface promoting activity-dependent synaptic reconnection. This multi-pronged approach illustrates an integrated platform with translational potential for CNS disorders in which circuit disconnection constrains recovery.
如何引用
AMA
Shiqiang Tong, Shuai Ye, Fenfen Ma, Xiaoying Xie, Yinzhe Sun, Chuchu Ma, et al. Self-assembling scaffolds epigenetically reactivate and electroactively guide neuronal regeneration to restore central neural circuits.. Nature communications. 2026; doi:10.1038/s41467-026-72397-6.
APA
Shiqiang Tong, Shuai Ye, Fenfen Ma, Xiaoying Xie, Yinzhe Sun, Chuchu Ma, et al (2026). Self-assembling scaffolds epigenetically reactivate and electroactively guide neuronal regeneration to restore central neural circuits.. Nature communications. https://doi.org/10.1038/s41467-026-72397-6
GB/T 7714
Shiqiang Tong, Shuai Ye, Fenfen Ma, Xiaoying Xie, Yinzhe Sun, Chuchu Ma, et al. Self-assembling scaffolds epigenetically reactivate and electroactively guide neuronal regeneration to restore central neural circuits.[J]. Nature communications, 2026 doi:10.1038/s41467-026-72397-6.
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