Biology subjects

Hong, J. T.

Publications and source records attributed to Hong, J. T..

2 recordsLinked to original sources

bioRxiv2016

Parkin knockout inhibits neuronal development via regulation of proteasomal degradation of p21

PARK2 encodes for the E3 ubiquitin ligase parkin and iimplicates in the development of Parkinsons disease (PD). Although the neuroprotective role of parkin is well known, the mechanism of parkins function in neural stem differentiation is not clear. Co-expressions network analysis showed that SNAP25 and BDNF were positively correlated with parkin, but negatively correlated with p21 in human patient brain. Therefore, we investigated a link between the ubiquitin E3 ligase parkin and proteasomal degradation of p21 for the control of neural stem cell differentiation. We discovered that p21 directly binds with parkin and is ubiquitinated by parkin resulting in the loss of cell differentiation ability. Tranfection of p21 shRNA in PARK2 KO mice significantly rescued the differentiation efficacy as well as SNAP25 and BDNF expression. We also defined the decreased p21 ubiquitination and differentiation ability were reversed after treatment with JNK inhibitor, SP600125 in PARK2 KO mice derived neural stem cells. Thus, the present study indicated that parkin knockout inhibits neural stem cell differentiation by JNK-dependent proteasomal degradation of p21.\n\nSummary statementThe present study indicated that parkin knockout inhibits neural stem cell differentiation by JNK-dependent proteasomal degradation of p21.

cell biology↗

bioRxiv2016

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

Impaired 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.

developmental biology↗