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Neuronal conversion from glia to replenish the lost neurons

Liang, Shiyu ; Zhou, Jing ; Yu, Xiaolin ; Lu, Shuai ; Liu, Ruitian

Neural regeneration research, 2024-07, Vol.19 (7), p.1446-1453 [Periódico revisado por pares]

India: Medknow Publications & Media Pvt. Ltd

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  • Título:
    Neuronal conversion from glia to replenish the lost neurons
  • Autor: Liang, Shiyu ; Zhou, Jing ; Yu, Xiaolin ; Lu, Shuai ; Liu, Ruitian
  • Assuntos: astrocytes; neural stem cells; neurodegenerative diseases; neuron; polypyrimidine tract binding protein 1; repair; reprogramming; small molecule; transcription factor; transdifferentiation ; Disease ; Neurons ; Review ; Transcription factors
  • É parte de: Neural regeneration research, 2024-07, Vol.19 (7), p.1446-1453
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Both authors contributed equally to this work.
    Author contributions: Literature search and manuscript draft: SL and JZ; manuscript revision and supervision: RL, XY and SL. All authors have read and approved the final version of the manuscript.
  • Descrição: Neuronal injury, aging, and cerebrovascular and neurodegenerative diseases such as cerebral infarction, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Huntington's disease are characterized by significant neuronal loss. Unfortunately, the neurons of most mammals including humans do not possess the ability to self-regenerate. Replenishment of lost neurons becomes an appealing therapeutic strategy to reverse the disease phenotype. Transplantation of pluripotent neural stem cells can supplement the missing neurons in the brain, but it carries the risk of causing gene mutation, tumorigenesis, severe inflammation, and obstructive hydrocephalus induced by brain edema. Conversion of neural or non-neural lineage cells into functional neurons is a promising strategy for the diseases involving neuron loss, which may overcome the above-mentioned disadvantages of neural stem cell therapy. Thus far, many strategies to transform astrocytes, fibroblasts, microglia, Müller glia, NG2 cells, and other glial cells to mature and functional neurons, or for the conversion between neuronal subtypes have been developed through the regulation of transcription factors, polypyrimidine tract binding protein 1 (PTBP1), and small chemical molecules or are based on a combination of several factors and the location in the central nervous system. However, some recent papers did not obtain expected results, and discrepancies exist. Therefore, in this review, we discuss the history of neuronal transdifferentiation, summarize the strategies for neuronal replenishment and conversion from glia, especially astrocytes, and point out that biosafety, new strategies, and the accurate origin of the truly converted neurons in vivo should be focused upon in future studies. It also arises the attention of replenishing the lost neurons from glia by gene therapies such as up-regulation of some transcription factors or down-regulation of PTBP1 or drug interference therapies.
  • Editor: India: Medknow Publications & Media Pvt. Ltd
  • Idioma: Inglês
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