Cited by 16Neurogenesis and neuroplasticity mechanismsPluripotent Stem Cells ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Therapeutic Potential of PTB Inhibition Through Converting Glial Cells to Neurons in the Brain

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Fu, Xiang-Dong, Mobley, William C.·2023·Annual Review of Neuroscience

DOI 10.1146/annurev-neuro-083022-113120

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Abstract

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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See all 16

Authors: Fu, X.-D., & Mobley, W. C.
Affiliations: Westlake University (CN)
University of California San Diego (US)
ORCID: Fu, Xiang-Dong
Mobley, William C.
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
DOI: 10.1146/annurev-neuro-083022-113120
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
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
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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Therapeutic Potential of PTB Inhibition Through Converting Glial Cells to Neurons in the Brain

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