Reversing Parkinson Disease Model with in situ Converted Nigral Neurons

@article{Qian2020ReversingPD,
  title={Reversing Parkinson Disease Model with in situ Converted Nigral Neurons},
  author={Hao Qian and Xinjiang Kang and Jing Hu and Dongyang Zhang and Zhengyu Liang and Fan Meng and Xuan Zhang and Yuanchao Xue and Roy Maimon and Steven F. Dowdy and Neal K. Devaraj and Zhuan Zhou and William C. Mobley and Don W. Cleveland and Xiang-Dong Fu},
  journal={Nature},
  year={2020},
  volume={582},
  pages={550 - 556}
}
Parkinson’s disease is characterized by loss of dopamine neurons in the substantia nigra 1 . Similar to other major neurodegenerative disorders, there are no disease-modifying treatments for Parkinson’s disease. While most treatment strategies aim to prevent neuronal loss or protect vulnerable neuronal circuits, a potential alternative is to replace lost neurons to reconstruct disrupted circuits 2 . Here we report an efficient one-step conversion of isolated mouse and human astrocytes to… 
Reversing a Model of Parkinson's Disease With In Situ Converted Nigral Neurons
  • Z. Israel, N. Asch
  • Biology
    Movement disorders : official journal of the Movement Disorder Society
  • 2020
TLDR
The successful one-step conversion of isolated mouse and human astrocytes to functional neurons by depletion of PTB in vitro is described, which has the potential not only to restore dopamine levels in the striatum but also to restore functionally normal circuitry.
Stem Cell-Based Therapies for Parkinson Disease
TLDR
Current understanding of the molecular pathogenesis of neurodegeneration in PD is summarized and the development of new therapeutic strategies that have led to the initiation of exploratory clinical trials are discussed, focusing on the applications of stem cells for the treatment of PD.
In vivo Direct Conversion of Astrocytes to Neurons Maybe a Potential Alternative Strategy for Neurodegenerative Diseases
TLDR
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) are summarized.
Current Approaches and Molecular Mechanisms for Directly Reprogramming Fibroblasts Into Neurons and Dopamine Neurons
TLDR
Recent progress in methods, mechanisms, and future challenges of directly reprogramming somatic fibroblasts into neurons or dopamine neurons were summarized to speed up the clinical translation of these directly converted neural cells to treat PD and other neurodegenerative diseases.
Human Neural Stem Cells Differentiate and Integrate, Innervating Implanted zQ175 Huntington’s Disease Mouse Striatum
TLDR
It is shown that 8-month implantation of hNSCs into the striatum of zQ175 HD mice ameliorates behavioral deficits, increases brain-derived neurotrophic factor (BDNF) and reduces mutant Huntingtin (mHTT) accumulation, and the findings support hN SC transplantation for further evaluation and clinical development for HD.
Brain Alchemy: Transforming Astrocytes into Neurons for Neurodegenerative Disease
TLDR
Astrocyte-to-neuron conversion is not only able to restore lost dopamine function in the nigrostriatal circuit but also can reverse the motor phenotype associated with dopamine depletion, marking an important milestone in the search for a cure for Parkinson’s disease and other neurodegenerative disorders.
Parkinson's disease motor symptoms rescue by CRISPRa‐reprogramming astrocytes into GABAergic neurons
TLDR
A knock‐in mouse line carrying a dual dCas9 transactivator system allowing the conditional in vivo activation of endogenous genes and an AAV‐dCAS approach to enable an alternative route for clinical therapies of Parkinson's disease suggest a novel intervention strategy beyond the restoration of dopamine levels.
Characterization of substantia nigra neurogenesis in homeostasis and dopaminergic degeneration: beneficial effects of the microneurotrophin BNN-20
TLDR
The results demonstrate the existence of a neurogenic system in the SNpc that can be manipulated in order to regenerate the depleted dopaminergic cell population in the “weaver” PD mouse model and Microneurotrophin BNN-20 emerges as an excellent candidate for future PD cell replacement therapies, due to its area-specific, pro-neurogenic effects.
Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease
TLDR
Current approaches to assess Neurogenesis and prospects in the application of optogenetic protocols to restore the neurogenesis in Parkinson’s disease are mainly focused on.
Astrocyte dysfunction in Parkinson's disease: from the perspectives of transmitted α-synuclein and genetic modulation
TLDR
It is concluded that astrocyte replenishment is a valuable therapeutic approach in PD because it can be replenished and even converted to functional neurons.
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