Evaluation of fisetin as a potential inducer of mitochondrial biogenesis in SH-SY5Y neuronal cells

Document Type : Original Article


Department of Genetics and Bioengineering, Alanya Alaaddin Keykubat University, Alanya, Antalya, Turkey


Objective(s): Increasing evidence implicates impaired mitochondrial biogenesis as an important contributor to mitochondrial dysfunction, which plays a central role in the pathogenesis of neurodegenerative diseases including Parkinson’s disease (PD). For this reason, targeting mitochondrial biogenesis may present a promising therapeutic strategy for PD. The present study attempted to investigate the effects of fisetin, a dietary flavonoid, on mitochondrial biogenesis and the expression of PD-associated genes in neuronal cells.
Materials and Methods: The effects of fisetin on mitochondrial biogenesis were evaluated by three different approaches; PGC-1α and TFAM mRNA expressions by RT-qPCR, mitochondrial DNA (mtDNA) content by quantitative PCR and mitochondrial mass by MitoTracker staining. Next, a PCR array was performed to evaluate the effects of fisetin on the expression profile of PD-associated genes. Finally, the common targets of fisetin and PD were analyzed by in silico analyses
Results: The results demonstrated that fisetin treatment can increase PGC-1α and TFAM mRNA levels, mtDNA copy number, and mitochondrial mass in neuronal cells. Fisetin also altered the expressions of some PD-related genes involved in neuroprotection and neuronal differentiation. Moreover, the bioinformatics analyses suggested that the AKT1-GSK3B signaling might be responsible for the potential neuroprotective effects of fisetin.
Conclusion: Collectively, these results imply that fisetin could modulate some neuroprotective mechanisms including mitochondrial biogenesis, and may serve as a potential drug candidate for PD.


Main Subjects

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