TY - JOUR
T1 - Fibroblast Growth Factor 9 Stimulates Neuronal Length Through NF-kB Signaling in Striatal Cell Huntington’s Disease Models
AU - Yusuf, Issa Olakunle
AU - Chen, Hsiu Mei
AU - Cheng, Pei Hsun
AU - Chang, Chih Yi
AU - Tsai, Shaw Jenq
AU - Chuang, Jih Ing
AU - Wu, Chia Ching
AU - Huang, Bu Miin
AU - Sun, H. Sunny
AU - Chen, Chuan Mu
AU - Yang, Shang Hsun
N1 - Funding Information:
This work was supported by the Ministry of Science and Technology (MOST 105-2628-B-006-015-MY3, 108-2314-B-006-079-MY3, and MOST 106-2320-B-006-004).
Funding Information:
IOY, HMC, PHC, and CYC handled the cellular studies and molecular analysis and analyzed the data; SJT, JIC, CCW, BMH, HSS, CMC, and SHY designed the experiments and oversaw the progress of the study. IOY, HMC, and SHY drafted the paper. All authors read and approved the final manuscript.
Publisher Copyright:
© 2021, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/5
Y1 - 2021/5
N2 - Proper development of neuronal cells is important for brain functions, and impairment of neuronal development may lead to neuronal disorders, implying that improvement in neuronal development may be a therapeutic direction for these diseases. Huntington’s disease (HD) is a neurodegenerative disease characterized by impairment of neuronal structures, ultimately leading to neuronal death and dysfunctions of the central nervous system. Based on previous studies, fibroblast growth factor 9 (FGF9) may provide neuroprotective functions in HD, and FGFs may enhance neuronal development and neurite outgrowth. However, whether FGF9 can provide neuronal protective functions through improvement of neuronal morphology in HD is still unclear. Here, we study the effects of FGF9 on neuronal length in HD and attempt to understand the related working mechanisms. Taking advantage of striatal cell lines from HD knock-in mice, we found that FGF9 increases total neuronal length and upregulates several structural and synaptic proteins under HD conditions. In addition, activation of nuclear factor kappa B (NF-kB) signaling by FGF9 was observed to be significant in HD cells, and blockage of NF-kB leads to suppression of these structural and synaptic proteins induced by FGF9, suggesting the involvement of NF-kB signaling in these effects of FGF9. Taken these results together, FGF9 may enhance total neuronal length through upregulation of NF-kB signaling, and this mechanism could serve as an important mechanism for neuroprotective functions of FGF9 in HD.
AB - Proper development of neuronal cells is important for brain functions, and impairment of neuronal development may lead to neuronal disorders, implying that improvement in neuronal development may be a therapeutic direction for these diseases. Huntington’s disease (HD) is a neurodegenerative disease characterized by impairment of neuronal structures, ultimately leading to neuronal death and dysfunctions of the central nervous system. Based on previous studies, fibroblast growth factor 9 (FGF9) may provide neuroprotective functions in HD, and FGFs may enhance neuronal development and neurite outgrowth. However, whether FGF9 can provide neuronal protective functions through improvement of neuronal morphology in HD is still unclear. Here, we study the effects of FGF9 on neuronal length in HD and attempt to understand the related working mechanisms. Taking advantage of striatal cell lines from HD knock-in mice, we found that FGF9 increases total neuronal length and upregulates several structural and synaptic proteins under HD conditions. In addition, activation of nuclear factor kappa B (NF-kB) signaling by FGF9 was observed to be significant in HD cells, and blockage of NF-kB leads to suppression of these structural and synaptic proteins induced by FGF9, suggesting the involvement of NF-kB signaling in these effects of FGF9. Taken these results together, FGF9 may enhance total neuronal length through upregulation of NF-kB signaling, and this mechanism could serve as an important mechanism for neuroprotective functions of FGF9 in HD.
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U2 - 10.1007/s12035-020-02220-w
DO - 10.1007/s12035-020-02220-w
M3 - Article
C2 - 33421017
AN - SCOPUS:85098964639
SN - 0893-7648
VL - 58
SP - 2396
EP - 2406
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 5
ER -