Potential of Neural Stem Cell-Based Therapy for Parkinson’s Disease

Chou, Chung-Hsing; Fan, Hueng Chuen; Hueng, Dueng-Yuan

doi:10.1155/2015/571475

Cited by 24 publications

(19 citation statements)

References 86 publications

(89 reference statements)

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“…Given that a small pool of neural stem cells are a potential source for replacing degenerated neurons in PD patients [50], we generated NPC lines from a normal or PD patient–derived SNCA-tri iPSC cells and characterized the NPCs with appropriate markers (Fig. 7A–C).…”

Section: Resultsmentioning

confidence: 99%

Chromatin-Bound Oxidized α-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson’s Disease

Vasquez

Mitra

Hegde

et al. 2017

JAD

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Alpha-synuclein (α-Syn) overexpression and misfolding/aggregation in degenerating dopaminergic neurons have long been implicated in Parkinson’s disease (PD). The neurotoxicity of α-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Although α-Syn is predominantly localized in presynaptic nerve terminals, a small fraction exists in neuronal nuclei. However, the functional and/or pathological role of nuclear α-Syn is unclear. Following up on our earlier report that α-Syn directly binds DNA in vitro, here we confirm the nuclear localization and chromatin association of α-Syn in neurons using proximity ligation and chromatin immunoprecipitation analysis. Moderate (~2-fold) increase in α-Syn expression in neural lineage progenitor cells (NPC) derived from induced pluripotent human stem cells (iPSCs) or differentiated SHSY-5Y cells caused DNA strand breaks in the nuclear genome, which was further enhanced synergistically by Fe salts. Furthermore, α-Syn required nuclear localization for inducing genome damage as revealed by the effect of nucleus versus cytosol-specific mutants. Enhanced DNA damage by oxidized and misfolded/oligomeric α-Syn suggests that DNA nicking activity is mediated by the chemical nuclease activity of an oxidized peptide segment in the misfolded α-Syn. Consistent with this finding, a marked increase in Fe-dependent DNA breaks was observed in NPCs from a PD patient-derived iPSC line harboring triplication of the SNCA gene. Finally, α-Syn combined with Fe significantly promoted neuronal cell death. Together, these findings provide a novel molecular insight into the direct role of α-Syn in inducing neuronal genome damage, which could possibly contribute to neurodegeneration in PD.

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Section: Resultsmentioning

confidence: 99%

Chromatin-Bound Oxidized α-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson’s Disease

Vasquez

Mitra

Hegde

et al. 2017

JAD

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“…In adults, NSCs are localized in the sub-ventricular zone (SVZ) and hippocampus [21,22]. As with drug therapy, many studies have suggested that NSC transplantation improves cognitive behaviour in animal models of AD [23], Parkinson's disease [24,25] Huntington's disease [26,27], amyotrophic lateral sclerosis [28] and other neurodegenerative diseases. After transplantation, NSCs differentiate into neurons and/or glial cells and release trophic factors.…”

Section: Neural Stem Cellsmentioning

confidence: 99%

Effects of neural stem cell transplantation in Alzheimer’s disease models

et al. 2020

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Currently there are no therapies for treating Alzheimer's disease (AD) that can effectively halt disease progression. Existing drugs such as acetylcholinesterase inhibitors or NMDA receptor antagonists offers only symptomatic benefit. More recently, transplantation of neural stem cells (NSCs) to treat neurodegenerative diseases, including AD, has been investigated as a new therapeutic approach. Transplanted cells have the potential to replace damaged neural circuitry and secrete neurotrophic factors to counter symptomatic deterioration or to alter lesion protein levels. However, since there are animal models that can recapitulate AD in its entirety, it is challenging to precisely characterize the positive effects of transplanting NSCs. In the present review, we discuss the types of mouse modeling system that are available and the effect in each model after human-derived NSC (hNSC) or murine-derived NSC (mNSC) transplantation. Taken together, results from studies involving NSC transplantation in AD models indicate that this strategy could serve as a new therapeutic approach.

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“…Local factors within the microenvironment of transplanted NSCs affect the fate of the cells, as measured by survival, proliferation, differentiation, and neurogenesis [67]. Several groups have studied modulation of stem cells or DA cells with combined cellular transplantation in animal models of PD ( Table 1) [68]. Besides the attempt to replace damaged tissues, it was shown that grafted cells may promote endogenous vasculogenesis and neurogenesis in the neighboring tissues [69].…”

Section: Restoration Of the Disrupted Neurovascular Microenvironment mentioning

confidence: 99%

Development of Neural Stem Cell-Based Therapies for Parkinson’s Disease

Lee¹,

Tsai²,

Chou³

2018

Parkinson's Disease - Understanding Pathophysiology and Developing Therapeutic Strategies

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Neural stem cell (NSC)-based therapies, such as cell transplantation, are an emerging strategy for restoring neuronal function in Parkinson's disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Advanced researches on the microenvironment of grafted cells will promote clinical applications of NSCs for neurological disorders. A novel cell culture model of the neurovascular network was therefore devised to investigate autocrine, paracrine, and juxtacrine signaling in the neurovascular unit generated by NSCs and vascular endothelial cells. Preclinical studies using cutting-edge technologies, including cellular reprogramming, advancement in scaffolds for brain tissue engineering, image-guided injection, and noninvasive monitoring of tissue regeneration will pave the way for successful clinical trials of NSC-based therapies for PD. Once the implanted or regenerated DA neurons are integrated into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.

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Potential of Neural Stem Cell-Based Therapy for Parkinson’s Disease

Cited by 24 publications

References 86 publications

Chromatin-Bound Oxidized α-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson’s Disease

Chromatin-Bound Oxidized α-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson’s Disease

Effects of neural stem cell transplantation in Alzheimer’s disease models

Development of Neural Stem Cell-Based Therapies for Parkinson’s Disease

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