TY - JOUR
T1 - Therapeutic Potential of PTBP1 Inhibition, If Any, Is Not Attributed to Glia-to-Neuron Conversion
AU - Wang, Lei Lei
AU - Zhang, Chun Li
N1 - Funding Information:
We thank members of the Zhang laboratory for discussions. C.-L.Z. is a W.W. Caruth, Jr. Scholar in Biomedical Research. The work in the Zhang laboratory was supported by the Decherd Foundation, the Texas Alzheimer’s Research and Care Consortium, and National Institutes of Health grants (NS127375, NS099073, NS092616, NS111776, and NS117065).
Publisher Copyright:
Copyright © 2023 by the author(s).
PY - 2023/7/10
Y1 - 2023/7/10
N2 - 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.
AB - 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.
KW - Müller glia
KW - PTBP1 inhibition
KW - astrocytes
KW - dopaminergic neurons
KW - glia-to-neuron conversion
KW - reprogramming
KW - retina ganglion cells
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U2 - 10.1146/annurev-neuro-092822-083410
DO - 10.1146/annurev-neuro-092822-083410
M3 - Review article
C2 - 36750409
AN - SCOPUS:85163911950
SN - 0147-006X
VL - 46
SP - 1
EP - 15
JO - Annual Review of Neuroscience
JF - Annual Review of Neuroscience
ER -