The DOI matches its Crossref record; 106 of the 106 references it cites were found in a registry or an index.
Therapeutic Potential of PTB Inhibition Through Converting Glial Cells to Neurons in the Brain
Open accessAbstract
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.
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“Accordingly, PTBP1 reduction can relieve this repression, resulting in transient PTBP2 upregulation and a shift toward a neuronal splicing landscape.”
From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [24]
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The Glial Nature of Embryonic and Adult Neural Stem Cells
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- Yang G, Yan Z, Wu X, Zhang M, Xu C, et al. 2022. Ptbp1 knockdown in mouse striatum did not induce astrocyte-to-neuron conversion using HA-tagged labeling system. bioRxiv 2022.2003.2029.486202. https://doi.org/10.1101/2022.03.29.486202 · DOI
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Mao, S., Qiao, R., Wang, Q., Shen, L., Li, D., Huo, X., Wang, J., Liu, K., Chen, W., Zhu, T., et al. (2025) · MedComm · doi:10.1002/mco2.70329 · Cited by 17
McDowall, S., Bagda, V., Hodgetts, S. I., Mastaglia, F. L., & Li, D. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00450-9 · Cited by 15
Liu, Y., Ren, J. M., Zhang, W., Ding, L., Ma, R., Zhang, M., Zheng, S., Liang, R., & Zheng, S. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122707 · Cited by 12
The perinucleolar compartment: structure, function, and utility in anti-cancer drug development
Makeyev, E. V., & Huang, S. (2024) · Nucleus · doi:10.1080/19491034.2024.2306777 · Cited by 12
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Metadata
- Authors
- Fu, X.-D., & Mobley, W. C.
- Affiliations
- Westlake University (CN)
- University of California San Diego (US)
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2023-07-10
- Volume
- 46
- Issue
- 1
- Pages
- 145-165
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- OpenAlex
- W4383815147
- Cited by
- 16
- References
- 106
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 1
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Annual Review of Neuroscience (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Larry L. Hillblom Foundation (2019-A-006-NET)
- National Institutes of Health
- National Institute on Aging (R01AG055523, R01AG070154, R01AG061151)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- PTBP1, RNA-binding proteins, astrocyte-to-neuron conversion, cell replacement therapy, Parkinson's disease, lineage tracing, neurodegenerative diseases, transcription factor overexpression
- MeSH terms
- Astrocytes, Brain, Humans, Neuroglia, Neurons, Parkinson Disease
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