TLR7/8 in the Pathogenesis of Parkinson’s Disease

Campolo, Michela; Filippone, Alessia; Biondo, Carmelo; Mancuso, Giuseppe; Casili, Giovanna; Lanza, Marika; Cuzzocrea, Salvatore; Esposito, Emanuela; Paterniti, Irene

doi:10.3390/ijms21249384

Cited by 26 publications

(30 citation statements)

References 62 publications

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“…Immunohistochemistry (IHC) staining for vascular endothelial growth factor (VEGF) and CD34 was measured in the lung tissues as previously described [62]. Briefly, lung sections (7 μm) were processed and incubated overnight with anti-VEGF polyclonal antibody (Santa Cruz Biotechnology; 1:500 #sc7269 in PBS, v/v, MA, USA) and anti-Caspase-3 (Santa Cruz Biotechnology; 1:500 #sc7272 in PBS, v/v, MA, USA).…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

The protective role of Prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion

et al. 2021

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Intestinal ischemia-reperfusion (II/R) develops when the blood flow to the intestines decreases, followed by the reestablishment of the blood supply to the ischemic tissue, resulting in intestinal mucosal barrier dysfunction, with consequent severe local and systemic inflammation. Acute lung injury (ALI) represents the most serious complication after II/R. KYP-2047 is a selective inhibitor of prolyl oligopeptidase (POP), a serine protease involved in the release of pro-angiogenic and inflammatory molecules. The aim of the present study is to assess the effects of POP-inhibition mediated by KYP-2047 treatment in the pathophysiology of ALI following II/R. An in vivo model of II/R was performed and mice were subjected to KYP-2047 treatment (intraperitoneal, 1, 2.5 and 5 mg/ kg). Histological analysis, Masson's trichrome staining, immunohistochemical, immunofluorescence, biochemical and western blots analysis were performed on ileum and lung samples. KYP-2047 treatment ameliorated histological alteration in ileum and lung, reduced collagen amount and lowered inflammatory protein levels. Moreover, TGF-β1, eNOS, VEGF and CD34 positive staining has been modulated; also, a reduction in apoptosis expression was confirmed. This research revealed the strong anti-inflammatory potential of KYP-2047 associated to its modulatory role on angiogenesis and apoptosis, suggesting POP as a novel therapeutic target for ALI after II/R.

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Section: Immunohistochemical Analysismentioning

confidence: 99%

The protective role of Prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion

et al. 2021

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“…Field et al [103], Lincoln et al [104], Ziliotto et al [105], El Sharkawi et al [106], Cossins et al [107], Mirowska-Guzel et al [108], Asouri et al [109], Cardamone et al [110], Begovich et al [111], Bennetts et al [112], Iparraguirre et al [113] and Oldoni et al [114] reported that HLA-DPB1, HLA-DQA1, CCL18, CCL20, MMP7, IL1A, IL2RA, CYBB (cytochrome b-245 beta chain), PTPN22, HLA-DMB, ANXA2 and CHIT1expression were associated with progression of multiple sclerosis, but these genes might be liable for advancement of dementia. Chang et al [115], Jamshidi et al [116], Campolo et al [117], Bottero et al [118], Gao et al [119], Haga et al [120], Klaver et al [121], Greenbaum et al [122] and Aguirre et al [123] reported that expression of HLA-DQB1, HLA-DRA, TLR7, TLR8, PTPRC (protein tyrosine phosphatase receptor type C), OSMR (oncostatin M receptor), FABP5, LAMP2, CHRNA5 and IL13RA1 could be an index for Parkinson's disease progression, but these genes might be responsible for progression of dementia. Shmuel-Galia et al [152] presented that expression of TLR6, TYROBP (transmembrane immune signaling adaptor TYROBP), SERPINA1, CCR5, ANXA1, SLC7A2, HAMP (hepcidin antimicrobial peptide), TSLP (thymic stromal lymphopoietin), B2M, CXCR4, C3, KYNU (kynureninase), CASP1, CD14, TLR1, TLR2, TREM2, HCK (HCK proto-oncogene, Src family tyrosine kinase), MAOB (monoamine oxidase B), GPNMB (glycoprotein nmb), CP (ceruloplasmin), AP1S2, SMPD3, CXCL11, SHANK3, CRHR1, DRD4, NOTCH3 and GNB3 were associated with progression of dementia.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Vastrad¹,

Vastrad²

2021

Preprint

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To provide a better understanding of dementia at the molecular level, this study aimed to identify the genes and key pathways associated with dementia by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing dataset GSE153960 derived from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between patients with dementia and healthy controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein protein interaction (PPI) network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network was constructed, analyzed and visualized, with which the hub genes miRNAs and TFs nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic curve (ROC) analysis and RT PCR. A total of 948 DEGs were screened out, among which 475 genes were up regulated; while 473 were down regulated. Functional enrichment analyses indicated that DEGs were mainly involved in defense response, ion transport, neutrophil degranulation and neuronal system. The hub genes (CDK1, TOP2A, MAD2L1, RSL24D1, CDKN1A, NOTCH3, MYB, PWP2, WNT7B and HSPA12B) were identified from PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network. We identified a series of key genes along with the pathways that were most closely related with dementia initiation and progression. Our results provide a more detailed molecular mechanism for the advancement of dementia, shedding light on the potential biomarkers and therapeutic targets.

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“…Mice were killed 7 days after MPTP injection and their brains were harvested, sectioned, and processed. The dose of MPTP (80 mg/kg) used was based on previous in vivo studies [ 17 , 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…The dose and route of administration of SUN11602 were based on previous in vivo studies [ 14 , 17 ], on a large-scale dose studies performed in our laboratory, and considering the mice body surface area-based dosing.…”

Section: Methodsmentioning

confidence: 99%

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SUN11602, a bFGF mimetic, modulated neuroinflammation, apoptosis and calcium-binding proteins in an in vivo model of MPTP-induced nigrostriatal degeneration

Ardizzone

Bova

Casili

et al. 2022

J Neuroinflammation

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Background Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. PD etiopathogenesis is multifactorial and not yet fully known, however, the scientific world advised the establishment of neuroinflammation among the possible risk factors. In this field, basic fibroblast growth factor/fibroblast growth factor receptor-1 (bFGF/FGFR1) could be a promising way to treat CNS-mediated inflammation; unfortunately, the use of bFGF as therapeutic agent is limited by its side effects. The novel synthetic compound SUN11602 exhibited neuroprotective activities like bFGF. With this perspective, this study aimed to evaluate the effect of SUN11602 administration in a murine model of MPTP-induced dopaminergic degeneration. Methods Specifically, nigrostriatal degeneration was induced by intraperitoneal injection of MPTP (80 mg/kg). SUN11602 (1 mg/kg, 2.5 mg/kg, and 5 mg/kg) was administered daily by oral gavage starting from 24 h after the first administration of MPTP. Mice were killed 7 days after MPTP induction. Results The results obtained showed that SUN11602 administration significantly reduced the alteration of PD hallmarks, attenuating the neuroinflammatory state via modulation of glial activation, NF-κB pathway, and cytokine overexpression. Furthermore, we demonstrated that SUN11602 treatment rebalanced Ca2+ overload in neurons by regulating Ca2+-binding proteins while inhibiting the apoptotic cascade. Conclusion Therefore, in the light of these findings, SUN11602 could be considered a valuable pharmacological strategy for PD.

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TLR7/8 in the Pathogenesis of Parkinson’s Disease

Cited by 26 publications

References 62 publications

The protective role of Prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion

The protective role of Prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

SUN11602, a bFGF mimetic, modulated neuroinflammation, apoptosis and calcium-binding proteins in an in vivo model of MPTP-induced nigrostriatal degeneration

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