A holy grail of regenerative medicine is to replenish the cells that are lost due to disease. The adult mammalian central nervous system (CNS) has, however, largely lost such a regenerative ability. An emerging strategy for the generation of new neurons is through glia-to-neuron (GtN) conversion in vivo, mainly accomplished by the regulation of fate-determining factors. When inhibited, PTBP1, a factor involved in RNA biology, was reported to induce rapid and efficient GtN conversion in multiple regions of the adult CNS. Remarkably, PTBP1 inhibition was also claimed to greatly improve behaviors of mice with neurological diseases or aging. These phenomenal claims, if confirmed, would constitute a significant advancement in regenerative medicine. Unfortunately, neither GtN conversion nor therapeutic potential via PTBP1 inhibition was validated by the results of multiple subsequent replication studies with stringent methods. Here we review these controversial studies and conclude with recommendations for examining GtN conversion in vivo and future investigations of PTBP1.

中文翻译：

---

PTBP1 抑制的治疗潜力（如果有的话）并不归因于胶质细胞到神经元的转化

再生医学的一个圣杯是补充因疾病而损失的细胞。然而，成年哺乳动物的中枢神经系统（CNS）已很大程度上丧失了这种再生能力。生成新神经元的一种新兴策略是通过体内胶质细胞到神经元（GtN）的转换，主要通过命运决定因子的调节来完成。据报道，当抑制 PTBP1（参与 RNA 生物学的因子）时，可在成人中枢神经系统的多个区域诱导快速有效的 GtN 转化。值得注意的是，PTBP1 抑制也据称可以极大地改善患有神经系统疾病或衰老的小鼠的行为。这些惊人的说法如果得到证实，将构成再生医学的重大进步。不幸的是，GtN 转化和通过 PTBP1 抑制的治疗潜力均未通过后续多项严格方法复制研究的结果得到验证。在这里，我们回顾了这些有争议的研究，并总结了检查 GtN 体内转化和 PTBP1 未来研究的建议。