Issa O. Yusuf
Interdisciplinary Neuroscience Academia Sinica, Taiwan
Title: Fibroblast Growth Factor 9 Suppresses cell death through ERK signalling in Huntington’s disease
Biography
Biography: Issa O. Yusuf
Abstract
Statement of Problem: Huntington’s disease (HD) is a heritable neurodegenerative disorder characterized by selective and progressive damage of medium spiny neurons in the striatum, and there is no cure for HD to date. A type of fibroblast growth factor (FGF), FGF9, has been reported to play prosurvival roles, in other neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. With many similarities in the cellular and pathological mechanisms that eventually cause cell death in neurodegenerative diseases, we hypothesize that FGF9 might provide neuroprotective functions in HD. Methods and Findings: Here, we used STHdhQ7/Q7 (WT) and STHdhQ111/Q111 (HD) striatal knock-in cell lines as our models, and examined the neuroprotective effects of FGF9 on HD. Employing MTT and PI staining assays to determine cell proliferation and survival respectively, we found that FGF9 enhanced cell proliferation and also increased cell survival under a starvation stress condition. In addition, we observed that FGF9 significantly upregulated FGF signalling through ERK1/2, Akt, JNK, and mTOR pathways, and increased neurotrophic factor (GDNF) and anti-apoptotic BcL-xL proteins in HD cells. Especially, ERK pathway plays a critical role in the effects of FGF9 on cell survival and GDNF regulation. Conclusion and Significance: These results not only show the neuroprotective effects of FGF9, but also clarify the critical mechanisms in HD cells, further providing therapeutic potential of FGF9 in HD.