Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2810 - 2810

Published: March 4, 2022

Schizophrenia is a very complex syndrome involving widespread brain multi-dysconnectivity. marked by cognitive, behavioral, and emotional dysregulations. Recent studies suggest that inflammation in the central nervous system (CNS) immune dysfunction could have role pathogenesis of schizophrenia. This hypothesis supported immunogenetic evidence, higher incidence rate autoimmune diseases patients with The dysregulation WNT/β-catenin pathway associated involvement neuroinflammation Several shown there vicious positive interplay operating between oxidative stress. modulated WNT/β-catenin, which interacts NF-kB pathway; inflammatory factors (including IL-6, IL-8, TNF-α); stress such as glutamate; dopamine. Neuroinflammation increased levels PPARγ. In schizophrenia, expression PPAR-γ increased, whereas PPARα are downregulated. suggests metabolic-inflammatory imbalance occurs this disorder. Thus, research’s triptych be novel therapeutic approach to counteract both

Language: Английский

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Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Jan. 21, 2022

The protein kinase, GSK-3, participates in diverse biological processes and is now recognized a promising drug discovery target treating multiple pathological conditions. Over the last decade, range of newly developed GSK-3 inhibitors chemotypes inhibition modes has been developed. Even more conspicuous dramatic increase indications that were tested from mood behavior disorders, autism cognitive disabilities, to neurodegeneration, brain injury pain. Indeed, clinical pre-clinical studies largely expanded uncovering new mechanisms novel insights into contribution neurodegeneration central nerve system (CNS)-related disorders. In this review we summarize developments field describe use variety CNS This remarkable volume information being generated undoubtedly reflects great interest, as well intense hope, developing potent safe practice.

Language: Английский

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Mapping the signaling network of BIN2 kinase using TurboID-mediated biotin labeling and phosphoproteomics

The Plant Cell, Journal Year: 2023, Volume and Issue: 35(3), P. 975 - 993

Published: Jan. 20, 2023

Elucidating enzyme-substrate relationships in posttranslational modification (PTM) networks is crucial for understanding signal transduction pathways but technically difficult because interactions tend to be transient. Here, we demonstrate that TurboID-based proximity labeling (TbPL) effectively and specifically captures the substrates of kinases phosphatases. TbPL-mass spectrometry (TbPL-MS) identified over 400 proximal proteins Arabidopsis thaliana BRASSINOSTEROID-INSENSITIVE2 (BIN2), a member GLYCOGEN SYNTHASE KINASE 3 (GSK3) family integrates signaling controlling diverse developmental acclimation processes. A large portion BIN2-proximal showed BIN2-dependent phosphorylation vivo or vitro, suggesting these are BIN2 substrates. Protein-protein interaction network analysis include interactors substrates, revealing high level among proteins. Our proteomic establishes uncovers functions regulating key cellular processes such as transcription, RNA processing, translation initiation, vesicle trafficking, cytoskeleton organization. We further discovered significant overlap between GSK3 phosphorylome O-GlcNAcylome, an evolutionarily ancient relationship nutrient-sensing O-glycosylation pathway. work presents powerful method mapping PTM networks, dataset kinase important insights into controls underlying plant growth acclimation.

Language: Английский

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Alternative transcription exceeds alternative splicing in generating the transcriptome diversity of cerebellar development

Genome Research, Journal Year: 2011, Volume and Issue: 21(8), P. 1260 - 1272

Published: June 28, 2011

Despite our growing knowledge that many mammalian genes generate multiple transcript variants may encode functionally distinct protein isoforms, the transcriptomes of various tissues and their developmental stages are poorly defined. Identifying transcriptome its regulation in a cell/tissue is key to deciphering cell/tissue-specific functions gene. We built genome-wide inventory noncoding protein-coding transcripts (transcriptomes), promoters (promoteromes) histone modification states (epigenomes) for developing, adult cerebella using integrative massive-parallel sequencing bioinformatics approach. The data consists 61,525 (12,796 novel) mRNAs transcribed by 29,589 (4792 corresponding 15,669 7624 genes. Importantly, results show from gene predominantly generated alternative transcriptional rather than splicing mechanisms, highlighting terminations as major sources diversity. Moreover, H3K4me3, not H3K27me3, defined use promoters, we identified combinatorial role H3K4me3 H3K27me3 regulating expression transcripts, including during development. observed strong bias both CpG-rich an exponential relationship between enrichment expression. Furthermore, majority associated with neurological diseases expressed through demonstrated aberrant medulloblastoma, cancer arising cerebellum. developing presented this study emphasize importance analyzing function at isoform level.

Language: Английский

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PTEN signaling in autism spectrum disorders

Current Opinion in Neurobiology, Journal Year: 2012, Volume and Issue: 22(5), P. 873 - 879

Published: June 2, 2012

Language: Английский

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