Abstract
Partly because of extensions in lifespan, the incidence of neurodegenerative diseases is increasing, while there is no effective approach to slow or prevent neuronal degeneration. As we all know, neurons cannot self-regenerate and may not be replaced once being damaged or degenerated in human brain. Astrocytes are widely distributed in the central nervous system (CNS) and proliferate once CNS injury or neurodegeneration occur. Actually, direct reprogramming astrocytes into functional neurons has been attracting more and more attention in recent years. Human astrocytes can be successfully converted into neurons in vitro. Notably, in vivo direct reprogramming of astrocytes into functional neurons were achieved in the adult mouse and non-human primate brains. In this review, we briefly summarized in vivo direct reprogramming of astrocytes into functional neurons as regenerative strategies for CNS diseases, mainly focusing on neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD). We highlight and outline the advantages and challenges of direct neuronal reprogramming from astrocytes in vivo for future neuroregenerative medicine.
Highlights
Because of extensions in lifespan, the incidence of neurodegenerative diseases such as Alzheimer’s disease (AD), (Alzheimer’s disease facts and figures, Alzheimers Dement, 2021), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), is increasing, and these neurodegenerative diseases result in a heavy social and economic burden in the world
We briefly summarized in vivo direct reprogramming of astrocytes into functional neurons as regenerative strategies for central nervous system (CNS) diseases, mainly focusing on neurodegenerative diseases such as PD, AD, HD, and ALS
Astrocytes can be converted into dopaminergic neurons by high expressing three transcription factors (NeuroD1, Ascl1, and Lmx1a), and miR-218, collectively referred to as NeAL218 in mouse striatum (Fyfe, 2017; Rivetti di Val Cervo et al, 2017) or by depleting an RNA-binding protein called PTB in mouse striatum or substantia nigra (Qian et al, 2020; Zhou et al, 2020), which leads to behavioral improvement in a mouse model of PD
Summary
Because of extensions in lifespan, the incidence of neurodegenerative diseases such as Alzheimer’s disease (AD), (Alzheimer’s disease facts and figures, Alzheimers Dement, 2021), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), is increasing, and these neurodegenerative diseases result in a heavy social and economic burden in the world. Rivetti di Val Cervo et al (2017) reported a strategy that was able to generate induced dopaminergic neurons from human astrocytes with reprogramming efficiency reaching up to 16% in vitro by using overexpression of three transcription factors in a lentiviral vector, NeuroD1, Ascl1, and Lmx1a, and the microRNA miR-218, collectively called NeAL218.
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