Cell replacement therapy represents a promising approach for treating neurodegenerative diseases. Contrary to the common addition strategy to generate new neurons from glia by overexpressing a lineage-specific transcription factor(s), a recent study introduced a subtraction strategy by depleting a single RNA-binding protein, Ptbp1, to convert astroglia to neurons not only in vitro but also in the brain. Given its simplicity, multiple groups have attempted to validate and extend this attractive approach but have met with difficulty in lineage tracing newly induced neurons from mature astrocytes, raising the possibility of neuronal leakage as an alternative explanation for apparent astrocyte-to-neuron conversion. This review focuses on the debate over this critical issue. Importantly, multiple lines of evidence suggest that Ptbp1 depletion can convert a selective subpopulation of glial cells into neurons and, via this and other mechanisms, reverse deficits in a Parkinson's disease model, emphasizing the importance of future efforts in exploring this therapeutic strategy.

中文翻译：

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通过将神经胶质细胞转化为大脑中的神经元来抑制 PTB 的治疗潜力

细胞替代疗法是治疗神经退行性疾病的一种有前途的方法。与通过过度表达谱系特异性转录因子从神经胶质细胞生成新神经元的常见加法策略相反，最近的一项研究引入了一种减法策略，通过消耗单个 RNA 结合蛋白 Ptbp1，将星形胶质细胞转化为神经元，不仅在体外，但也存在于大脑中。鉴于其简单性，多个研究小组试图验证和扩展这种有吸引力的方法，但在从成熟星形胶质细胞中追踪新诱导的神经元时遇到了困难，这增加了神经元渗漏作为明显星形胶质细胞到神经元转换的另一种解释的可能性。本评论重点关注有关这一关键问题的争论。重要的是，多种证据表明 Ptbp1 缺失可以将选择性的神经胶质细胞亚群转化为神经元，并通过这种机制和其他机制逆转帕金森病模型中的缺陷，强调了未来努力探索这种治疗策略的重要性。