Therapeutic Potential of PTB Inhibition Through Converting Glial Cells to Neurons in the Brain
Year: 2023
Type: review
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.
Source: Annual Review of Neuroscience
Authors: Xiang-Dong Fu, William C. Mobley
Institutions: Westlake University, University of California San Diego
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Awards: Treating with Gamma-Secretase Modulators to Prevent Neurodegeneration in Mouse Models of Down Syndrome and Alzheimer Disease, G3466895947, Multiplexed Single Nucleus RNA and ATAC-seq Sequencing and Cortical Organoids: Transformative Insights into Down Syndrome, Antisense Oligonucleotides targeting APP to prevent neurodegeneration in models of Down Syndrome and Alzheimer's disease
OpenAlex ID: W4383815147