Covering the Role of PGC-1α in the Nervous System

Kuczynska, Zuzanna; Metin, Erkan; Liput, Michał; Bużañska, Leonora

doi:10.3390/cells11010111

Cited by 19 publications

(8 citation statements)

References 108 publications

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“…Downstream PGC-1α targets NRF1, NRF2, and mtTFA, which are key regulators of mitochondrial gene transcription and mtDNA replication, and their upregulation indicates enhanced mitochondrial biogenesis and function. Moreover, PGC-1α has been shown to play critical roles in regulating inflammation and M2 macrophage polarization ( 23 , 24 ). Exogenous expression of PGC-1α markedly enhanced macrophage recruitment and M2 skewing, whereas PGC-1α knockdown via siRNA abrogated this effect.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Tang,

Dong,

Wang

et al. 2024

Braz J Med Biol Res

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The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

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Section: Discussionmentioning

confidence: 99%

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Tang,

Dong,

Wang

et al. 2024

Braz J Med Biol Res

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“…In addition, the role of PGC-1α in the pathogenesis of age-related macular degeneration is related to direct or indirect interactions with vascular endothelial growth factor (VEGF), telomerase, oxidative stress, and autophagy-related mechanisms [ 49 ]. PGC-1α has unique roles in the central nervous system of mouse models, such as in the maturation of neuronal cells and synaptogenesis, while deficiencies promote behavioral dysfunction by impacting the inhibitory signals of dopaminergic and interneurons [ 50 ]. PCDH7 encodes the cadherin protein of brain–heart protocadherin (BHPCDH), which mediates calcium-dependent cell-cell adhesion [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Familial 4p Interstitial Deletion Provides New Insights and Candidate Genes Underlying This Rare Condition

Yenwongfai

Rieger

et al. 2023

Genes

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Chromosome 4p deletions can lead to two distinct phenotypic outcomes: Wolf-–Hirschhorn syndrome (a terminal deletion at 4p16.3) and less frequently reported proximal interstitial deletions (4p11-p16). Proximal 4p interstitial deletions can result in mild to moderate intellectual disability, facial dysmorphisms, and a tall thin body habitus. To date, only 35 cases of proximal 4p interstitial deletions have been reported, and only two of these cases have been familial. The critical region for this syndrome has been narrowed down to 4p15.33-15.2, but the underlying causative genes remain unclear. In this study, we report the case of a 3-year-old female with failure to thrive, developmental and motor delays, and morphological features. The mother also had a 4p15.2-p14 deletion, and the proband was found to have a 13.4-Mb 4p15.2-p14 deletion by chromosome microarray analysis. The deleted region encompasses 16 genes, five of which have a high likelihood of contributing to the phenotype: PPARGC1A, DHX15, RBPJ, STIM2, and PCDH7. These findings suggest that multiple genes are involved in this rare proximal 4p interstitial deletion syndrome. This case highlights the need for healthcare providers to be aware of proximal 4p interstitial deletions and the potential phenotypic manifestations.

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“…PGC-1α also participates in the procedure of synaptogenesis. PGC-1α can enhance the expression of synaptic proteins, such as PSD95 (47,48). In addition, PGC-1α is engaged in the process of macrophage polarization from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype and then participates in the inflammation responses (49,50).…”

Section: Discussionmentioning

confidence: 99%

Role of PGC-1α mediated synaptic plasticity, mitochondrial function, and neuroinflammation in the antidepressant effect of Zi-Shui-Qing-Gan-Yin

et al. 2023

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Depression is the most prevalent psychiatric disorder, which needs deeper mechanism research studies and effective therapy. Zi-Shui-Qing-Gan-Yin (ZSQGY) is a traditional Chinese medicine decoction that has been widely used in China in the treatment of depressive symptoms. The aim of the study was to examine the anti-depressive effects of ZSQGY and the possible mechanism of action in the monosodium glutamate (MSG)-induced depressive model and the corticosterone (CORT)-induced PC12 cell model. Liquid chromatography-mass spectrometry (LC–MS) was performed to determine the major compounds in the water extract of ZSQGY. The depressive behaviors were evaluated by the field swimming test (FST), the sucrose preference test (SPT), and the open field test (OFT). Golgi staining and transmission electron microscopy (TEM) were performed to display the alterations of synaptic ultrastructure. The mitochondrion function and inflammatory factors were also quantified. The changes in peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) expression were evaluated. The results of this study demonstrated that ZSQGY significantly improved depressive behaviors. ZSQGY also reversed the changes in synaptic plasticity, improved mitochondrion function, and reduced the levels of inflammatory factors. The neuroprotective effects were accompanied by the increased expression of PGC-1α. However, the beneficial changes were reversed after the inhibition of PGC-1α. These results indicated that ZSQGY effectively could improve depressive behaviors via the mechanisms that regulate synaptic structural plasticity, improve mitochondrion function, and alleviate neuroinflammation, which could, or partly, attribute to the regulation of PGC-1α.

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Covering the Role of PGC-1α in the Nervous System

Cited by 19 publications

References 108 publications

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Familial 4p Interstitial Deletion Provides New Insights and Candidate Genes Underlying This Rare Condition

Role of PGC-1α mediated synaptic plasticity, mitochondrial function, and neuroinflammation in the antidepressant effect of Zi-Shui-Qing-Gan-Yin

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