Abstract
The dopaminergic neuron degeneration and loss that occurs in Parkinson’s disease (PD) has been tightly linked to mitochondrial dysfunction. Although the aged-related cause of the mitochondrial defect observed in PD patients remains unclear, nuclear genes are of potential importance to mitochondrial function. Human peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) is a multi-functional transcription factor that tightly regulates mitochondrial biogenesis and oxidative capacity. The goal of the present study was to explore the potential pathogenic effects of interference by the PGC-1α gene on N-methyl-4-phenylpyridinium ion (MPP+)-induced SH-SY5Y cells. We utilized RNA interference (RNAi) technology to probe the pathogenic consequences of inhibiting PGC-1α in the SH-SY5Y cell line. Remarkably, a reduction in PGC-1α resulted in the reduction of mitochondrial membrane potential, intracellular ATP content and intracellular H2O2 generation, leading to the translocation of cytochrome c (cyt c) to the cytoplasm in the MPP+-induced PD cell model. The expression of related proteins in the signaling pathway (e.g., estrogen-related receptor α (ERRα), nuclear respiratory factor 1 (NRF-1), NRF-2 and Peroxisome proliferator-activated receptor γ (PPARγ)) also decreased. Our finding indicates that small interfering RNA (siRNA) interference targeting the PGC-1α gene could inhibit the function of mitochondria in several capacities and that the PGC-1α gene may modulate mitochondrial function by regulating the expression of ERRα, NRF-1, NRF-2 and PPARγ. Thus, PGC-1α can be considered a potential therapeutic target for PD.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by the progressive loss of dopaminergic neurons and affects more than 1% of the population older than 60 years of age (Abou-Sleiman et al, 2006)
To establish an MPP+-induced cell model of PD for investigating the potential pathogenic effects of PGC-1α on PD, we first examined whether SH-SY5Y cell could be eligible for a dopaminergic neuronal-like cell model of PD by expressing Tyrosine Hydroxylase (TH)
To explore which co-factors are involved in mitochondrial signal transduction, we examined the protein levels of PGC-1α, estrogen-related receptor α (ERRα), NRF-1, NRF-2, and PD-Liked DamagePeroxisome proliferator-activated receptor γ (PPARγ)
Summary
Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by the progressive loss of dopaminergic neurons and affects more than 1% of the population older than 60 years of age (Abou-Sleiman et al, 2006). NRF-1, NRF-2, ERRα and PPARγ are primarily responsible for regulating the expression of nuclear-encoded mitochondrial genes, including the components of complexes I-V, cytochrome c (cyt c) and mitochondrial transcription factor A (TFAM; Kelly and Scarpulla, 2004). Those nuclear-encoded mitochondrial genes are regulating the energy metabolism of the brain. PGC-1α is, believed to be a major regulator of mammalian mitochondrial biogenesis during physiological or pathological stress
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
