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Progress in Dopaminergic Cell Replacement and Regenerative Strategies for Parkinson's Disease

期刊

ACS CHEMICAL NEUROSCIENCE
卷 10, 期 2, 页码 839-851

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.8b00389

关键词

Parkinson's disease; dopaminergic neurons; embryonic stem cell; induced pluripotent stem cell; neural stem cell; direct lineage reprogramming; endogenous regeneration

资金

  1. Guangdong Provincial Key Laboratory of Brain Function and Disease [2014B-030301008]
  2. National Natural Science Foundation of China [31871019, 81471289, 81601104, 81771368]
  3. Natural Science Foundation of Guangdong Province [2017A-030313507, 2017A030313862]
  4. Science and Technology Project of Guangzhou City [201604020141, 2017-04020066, 201804020008]

向作者/读者索取更多资源

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder symptomatically characterized by resting tremor, rigidity, bradykinesia, and gait impairment. These motor deficits suffered by PD patients primarily result from selective dysfunction or loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). Most of the existing therapies for PD are based on the replacement of dopamine, which is symptomatically effective in the early stage but becomes increasingly less effective and is accompanied by serious side effects in the advanced stages of the disease. Currently, there are no strategies to slow neuronal degeneration or prevent the progression of PD. Thus, the prospect of regenerating functional dopaminergic neurons is very attractive. Over the last few decades, significant progress has been made in the development of dopaminergic regenerative strategies for curing PD. The most promising approach seems to be cell-replacement therapy (CRT) using human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), which are unlimitedly available and have gained much success in preclinical trials. Despite the challenges, stem cell-based CRT will make significant steps toward the clinic in the coming decade. Alternatively, direct lineage reprogramming, especially in situ direct conversion of glia cells to induced neurons, which exhibits some advantages including no ethical concerns, no risk of tumor formation, and even no need for transplantation, has gained much attention recently. Evoking the endogenous regeneration ability of neural stem cells (NSCs) is an idyllic method of dopaminergic neuroregeneration which remains highly controversial. Here, we review many of these advances, highlighting areas and strategies that might be particularly suited to the development of regenerative approaches that restore dopaminergic function in PD.

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