scholarly journals PRDX6 inhibits neurogenesis of neural precursor cells through downregulation of wdfy1 mediated TLR4 signal

2016 ◽  
Author(s):  
Mi Hee Park ◽  
Dong Ju Son ◽  
Kyoung Tak Nam ◽  
So Young Kim ◽  
Sang Yeon Oh ◽  
...  

AbstractImpaired neurogenesis has been associated with brain disorders. The role of peroxiredoxin 6 (PRDX6) in the neurodegenerative diseases is very controversial. To demonstrate the role of PRDX6 in neurogenesis, we compared neurogenesis ability and studied the molecular mechanisms. It was found that the neurogenesis of neural stem cells and expression of the marker protein were lowered in PRDX6 Tg-mice compared with non-tg mice. Moreover, the expression of wdfy1 was dramatically decreased in PRDX6-Tg mice, also, we observed that wdfy1 siRNA decreases the differentiation ability of primary neural stem cells to astrocyte and neuronal cells as well as PC12 cells. However, knockdown of PRDX6 recovered neurogenesis in the brain of PRDX6-Tg mice as well as PC-12 cells. We also showed that TLR4 was dramatically reduced in PRDX6 Tg mice as well as PC-12 cells and PRDX6 overexpression reduced neurogenesis was rescued after treatment of TLR4 siRNA. We further found that reduced TLR4 expression and neurogenesis was reversed in the neuron from PRDX6-Tg mice as well as PC12 cells by introduction of wdfy1 plasmid. Moreover, TLR4 siRNA reduced neurogenesis and wdfy1 expression. This study indicated that PRDX6 inhibits neurogenesis of neural precursor cells through TLR4 dependent downregulation of wdfy1.

PLoS ONE ◽  
2010 ◽  
Vol 5 (3) ◽  
pp. e9838 ◽  
Author(s):  
Mi-Yoon Chang ◽  
Dohoon Kim ◽  
Chun-Hyung Kim ◽  
Hoon-Chul Kang ◽  
Eungi Yang ◽  
...  

2005 ◽  
Vol 170 (5) ◽  
pp. 721-732 ◽  
Author(s):  
Phillip Karpowicz ◽  
Cindi Morshead ◽  
Angela Kam ◽  
Eric Jervis ◽  
John Ramunas ◽  
...  

The immortal strand hypothesis proposes that asymmetrically dividing stem cells (SCs) selectively segregate chromosomes that bear the oldest DNA templates. We investigated cosegregation in neural stem cells (NSCs). After exposure to the thymidine analogue 5-bromo-2-deoxyuridine (BrdU), which labels newly synthesized DNA, a subset of neural precursor cells were shown to retain BrdU signal. It was confirmed that some BrdU-retaining cells divided actively, and that these cells exhibited some characteristics of SCs. This asymmetric partitioning of DNA then was demonstrated during mitosis, and these results were further supported by real time imaging of SC clones, in which older and newly synthesized DNA templates were distributed asymmetrically after DNA synthesis. We demonstrate that NSCs are unique among precursor cells in the uneven partitioning of genetic material during cell divisions.


2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Seung-Hun Oh ◽  
Yong-Woo Jeong ◽  
Wankyu Choi ◽  
Jeong-Eun Noh ◽  
Suji Lee ◽  
...  

Stem cell therapy is a promising option for treating functional deficits in the stroke-damaged brain. Induced pluripotent stem cells (iPSCs) are attractive sources for cell therapy as they can be efficiently differentiated into neural lineages. Episomal plasmids (EPs) containing reprogramming factors can induce nonviral, integration-free iPSCs. Thus, iPSCs generated by an EP-based reprogramming technique (ep-iPSCs) have an advantage over gene-integrating iPSCs for clinical applications. However, there are few studies regarding the in vivo efficacy of ep-iPSCs. In this study, we investigated the therapeutic potential of intracerebral transplantation of neural precursor cells differentiated from ep-iPSCs (ep-iPSC-NPCs) in a rodent stroke model. The ep-iPSC-NPCs were transplanted intracerebrally in a peri-infarct area in a rodent stroke model. Rats transplanted with fibroblasts and vehicle were used as controls. The ep-iPSC-NPC-transplanted animals exhibited functional improvements in behavioral and electrophysiological tests. A small proportion of ep-iPSC-NPCs were detected up to 12 weeks after transplantation and were differentiated into both neuronal and glial lineages. In addition, transplanted cells promoted endogenous brain repair, presumably via increased subventricular zone neurogenesis, and reduced poststroke inflammation and glial scar formation. Taken together, these results strongly suggest that intracerebral transplantation of ep-iPSC-NPCs is a useful therapeutic option to treat clinical stroke through multimodal therapeutic mechanisms.


2018 ◽  
Vol 51 ◽  
pp. 14-23 ◽  
Author(s):  
Sandeep Kumar Vishwakarma ◽  
Nusrath Fatima ◽  
Chandrakala Lakkireddy ◽  
Nagarapu Raju ◽  
Avinash Bardia ◽  
...  

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