期刊
ANNUAL REVIEW OF NEUROSCIENCE
卷 46, 期 -, 页码 1-15出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-neuro-092822-083410
关键词
glia-to-neuron conversion; PTBP1 inhibition; astrocytes; dopaminergic neurons; Muller glia; retina ganglion cells; reprogramming
A key goal of regenerative medicine is to replenish lost cells due to disease. However, the adult mammalian central nervous system lacks regenerative ability. An emerging strategy for generating new neurons is glia-to-neuron conversion, mainly through the regulation of fate-determining factors. PTBP1 inhibition was thought to induce rapid and efficient glia-to-neuron conversion and improve behaviors in neurological diseases or aging, but subsequent replication studies failed to validate these claims.
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.
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