Peroxisome Proliferator-Activated Receptor-Gamma (PPAR-ɣ): Molecular Effects and Its Importance as a Novel Therapeutic Target for Cerebral Ischemic Injury

Mannan, Ashi; Garg, Nikhil; Singh, Thakur Gurjeet; Kang, Harmeet Kaur

doi:10.1007/s11064-021-03402-1

Cited by 36 publications

(16 citation statements)

References 254 publications

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“…Liu, Zhang 52 reported that NF-kB was activated by several stimuli including TNF-α, interferon-gamma (IFN-γ), interleukins, bacterial and viral infection. The inflammatory reaction initiated by the inflammatory cytokines as TNF-α promote the accumulation of inflammatory cells that express iNOS and yield vast quantities of NO 53 ; which was found to be elevated in the current study. Also, the activation of NF-κB highly expresses iNOS which continuously produces NO 54 .…”

Section: Discussionsupporting

confidence: 51%

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Molecular evidence of the amelioration of toluene induced encephalopathy by human breast milk mesenchymal stem cells

Hamid

Domouky

Elfakharany

2022

Sci Rep

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Toluene was widely used volatile organic compound that accumulates in tissues with high lipid content. Stem cells have been proposed as an increasingly attractive approach for repair of damaged nervous system, we aimed to evaluate the ability of breast milk mesenchymal stem cells (MSc) to ameliorate toluene-induced encephalopathy. Sixty adult male albino rats were assigned to 3 groups, control, toluene, and toluene/breast milk-MSc. Neurological assessment was evaluated as well as serum levels of glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-α), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), tissue dopamine and oxidative markers. Gene expression of peroxisome Proliferator-Activated Receptor-Gamma (PPAR-ɣ), nuclear factor-kappaB (NF-kB), and interleukin-6 (IL-6) were evaluated. Moreover, histological and immunohistochemical investigation were done. Results revealed that toluene caused cerebral injury, as evidenced by a significant increase in serum GFAP, TNF-α, malondialdehyde (MDA) and nitric oxide (NO), a significant decrease in serum NGF, tissue dopamine and oxidative markers, besides, a non-significant change in VEGF. Toluene also caused changes in normal cerebral structure and cellular degeneration, including a significant decrease in the total number of neurons and thickness of frontal cortex. Meninges showing signs of inflammation with inflammatory cell infiltration and exudation, a significant decrease in MBP immunoreactivity, and increase in the percent of high motility group box protein-1 (HMGB1) positive cells. PPAR- ɣ, NF-kB, and IL-6 gene expression were all considerably elevated by toluene. These changes were greatly improved by breast milk MSc. Therefore, we conclude that breast milk MSc can attenuate toluene-induced encephalopathy.

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Section: Discussionsupporting

confidence: 51%

“…In accordance, De Nuccio, Bernardo 70 suggested that PPAR-γ agonists promotes myelination via many mechanisms, including enhancing the functions of the mitochondria and affecting oscillatory Ca (2 +) waves. In addition, PPAR-ɣ also induces reduction of inflammation, inhibition of oxidative stress, decrease of pro-apoptotic factors 53 .…”

Section: Discussionmentioning

confidence: 99%

Molecular evidence of the amelioration of toluene induced encephalopathy by human breast milk mesenchymal stem cells

Hamid

Domouky

Elfakharany

2022

Sci Rep

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“…As mentioned above, "CAMs" and "leukocyte transendothelial migration" play crucial roles in regulating adhesion at inflammatory sites and in the immune response (30,31). It has been reported that PPAR activation can induce anti-inflammatory and antioxidant effects, provide vascular protection, and inhibit apoptosis in the nervous system; thus, PPAR may be a novel pharmacological target in neuroprotection (50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Quantitative iTRAQ proteomics reveal the proteome profiles of bone marrow mesenchymal stem cells after cocultures with Schwann cells in vitro

Ding¹,

Li²,

Sun³

et al. 2022

Ann Transl Med

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Background: Bone marrow mesenchymal stem cells (BMSCs) combined with Schwann cells (SCs) represent a better therapeutic cell transplantation strategy for treating spinal cord injury (SCI) than transplantation with BMSCs or SCs alone. In previous studies, we demonstrated that BMSCs are able to differentiate in neuron-like cells when cocultured with SCs. The detailed mechanism underlying SCI repair that occurs during the combined transplantation of BMSCs and SCs has not yet been studied. In this study, we adopted an isobaric tag for relative and absolute quantitation (iTRAQ)-based protein identification/ quantification approach to examine the effects of the SC and BMSC coculture process on the BMSCs and then obtained and analyzed the differentially expressed proteins (DEPs) and their possible related pathways.Methods: This study included three groups based on the number of coculture days (i.e., 0, 3, and 7 days).Changes in BMSC protein expression levels were measured using the iTRAQ technique. A bioinformatics analysis of all the data was performed.Results: In total, 6,760 types of proteins were detected, corresponding to 5,181 data points with quantitative information. Of these, a total of 243 DEPs were identified, of which 169 proteins were upregulated and 74 proteins were downregulated. These DEPs were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Intercellular adhesion molecule-1 (ICAM-1), integrin, and dioxygenase may play crucial roles in the repair of SCI. The data analysis indicates that the relevant biological processes may be regulated by lysosome function, cell adhesion molecules (CAMs), leukocyte transendothelial migration, and the phosphatidylinositol-3-kinase (PI3K) and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Conclusions:The data provided in this study indicate that several molecular mechanisms and signaling pathways are involved in the BMSC and SC coculture process. This information may be useful for the further identification of specific targets and related mechanisms and guide new directions for SCI treatment.

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“…This review has focused on targeting PPAR-γ in the PNS, however, there are studies that have explored targeting PPAR-γ in the CNS [76][77][78][79]. An evaluation of the published literature revealed that an extensive list of drugs or small molecules targeting PPAR-γ have been tested in injuries of the CNS (Table 2).…”

Section: Ppar-γ In the Central Nervous Systemmentioning

confidence: 99%

Repurposing Small Molecules to Target PPAR-γ as New Therapies for Peripheral Nerve Injuries

2021

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The slow rate of neuronal regeneration that follows peripheral nerve repair results in poor recovery, particularly where reinnervation of muscles is delayed, leading to atrophy and permanent loss of function. There is a clear clinical need to develop drug treatments that can accelerate nerve regeneration safely, restoring connections before the target tissues deteriorate irreversibly. The identification that the Rho/Rho-associated kinase (ROCK) pathway acts to limit neuronal growth rate is a promising advancement towards the development of drugs. Targeting Rho or ROCK directly can act to suppress the activity of this pathway; however, the pathway can also be modulated through the activation of upstream receptors; one of particular interest being peroxisome proliferator-activated receptor gamma (PPAR-γ). The connection between the PPAR-γ receptor and the Rho/ROCK pathway is the suppression of the conversion of inactive guanosine diphosphate (GDP)-Rho to active guanosine triphosphate GTP-Rho, resulting in the suppression of Rho/ROCK activity. PPAR-γ is known for its role in cellular metabolism that leads to cell growth and differentiation. However, more recently there has been a growing interest in targeting PPAR-γ in peripheral nerve injury (PNI). The localisation and expression of PPAR-γ in neural cells following a PNI has been reported and further in vitro and in vivo studies have shown that delivering PPAR-γ agonists following injury promotes nerve regeneration, leading to improvements in functional recovery. This review explores the potential of repurposing PPAR-γ agonists to treat PNI and their prospective translation to the clinic.

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Peroxisome Proliferator-Activated Receptor-Gamma (PPAR-ɣ): Molecular Effects and Its Importance as a Novel Therapeutic Target for Cerebral Ischemic Injury

Cited by 36 publications

References 254 publications

Molecular evidence of the amelioration of toluene induced encephalopathy by human breast milk mesenchymal stem cells

Molecular evidence of the amelioration of toluene induced encephalopathy by human breast milk mesenchymal stem cells

Quantitative iTRAQ proteomics reveal the proteome profiles of bone marrow mesenchymal stem cells after cocultures with Schwann cells in vitro

Repurposing Small Molecules to Target PPAR-γ as New Therapies for Peripheral Nerve Injuries

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