The Basic Requirement of Tight Junction Proteins in Blood-Brain Barrier Function and Their Role in Pathologies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5601 - 5601

Published: May 21, 2024

This review addresses the role of tight junction proteins at blood-brain barrier (BBB). Their expression is described, and their in physiological pathological processes BBB discussed. Based on this, new approaches are depicted for paracellular drug delivery diagnostics treatment cerebral diseases. Recent data provide convincing evidence that, addition to its impairment course diseases, could be involved aetiology CNS disorders. Further progress will expected based insights protein structure involvement signalling pathways.

Language: Английский

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Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood–Brain Barrier and Neuroinflammation

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

ABSTRACT Background Vascular dementia (VaD) includes a group of brain disorders that are characterized by cerebrovascular pathology.Neuroinflammation, disruption the blood–brain barrier (BBB) permeability, white matter lesions, and neuronal loss all significant pathological manifestations VaD play key role in disease progression. Necroptosis, also known asprogrammed necrosis, is mode programmed cell death distinct from apoptosis closely associated with ischemic injury neurodegenerative diseases. Recent studies have shown necroptosis exacerbates BBB destruction, activates neuroinflammation, promotes loss, severely affects prognosis. Results Conclusions In this review, we outline roles its molecular mechanisms process VaD, particular focus on modulating neuroinflammation exacerbating permeability elaborate regulatory centrally involved cells mediated tumor necrosis factor‐α VaD. We analyze possibility specific strategy targeting would help inhibit destruction With necroptosis, study delved into impact changes prognosis to provide new treatment ideas.

Language: Английский

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A window into intracellular events in myositis through subcellular proteomics

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 31, 2025

Abstract Objective and design Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of muscle disorders unknown etiology. It is postulated that mitochondrial dysfunction protein aggregation in skeletal contribute to myofiber degeneration. However, molecular pathways lead not well defined. Subjects Here we have isolated membrane-bound organelles (e.g., nuclei, mitochondria, sarcoplasmic/endoplasmic reticulum, Golgi apparatus, plasma membrane) from biopsies normal (n = 3) disease patients 11). Of the myopathy group, 10 displayed abnormalities (IIM 9); 1)), one IIM patient did show (polymyositis). Methods Global proteomic analysis was performed using an Orbitrap Fusion mass spectrometer. Upon unsupervised clustering, samples clustered separately samples. Results We confirmed previously known alterations identified several new ones. For example, found differential expression (i) nuclear proteins control cell division, transcription, RNA regulation, stability, (ii) ER involved folding, degradation, trafficking cytosol, (iii) energy production/metabolism cytoskeletal contractile machinery muscle. Conclusions Our data demonstrates limited aggregations cytosol (inclusions) occur nuclear, mitochondrial, membrane compartments

Language: Английский

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Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders

Discover Mental Health, Journal Year: 2025, Volume and Issue: 5(1)

Published: Feb. 22, 2025

Viral infections may disrupt the structural and functional integrity of nervous system, leading to acute conditions such as encephalitis, neuropsychiatric mood disorders, schizophrenia, neurodegenerative diseases. Investigating viral interactions human proteins reveal mechanisms underlying these effects offer insights for therapeutic interventions. This study explores molecular virus that be related disorders. Herpes Simplex Virus-1 (HSV-1), Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Influenza A (IAV) (H1N1, H5N1), Human Immunodeficiency (HIV1&2) were selected key viruses. Protein structures each accessed from Data Bank analyzed using HMI-Pred web server detect interface mimicry between proteins. The PANTHER classification system was used categorize viral-human protein based on function cellular localization. Energetically favorable identified HSV-1 (467), CMV (514), EBV (495), H1N1 (3331), H5N1 (3533), HIV 1&2 (62425). Besides immune apoptosis-related pathways, including those associated with Parkinson's Huntington's diseases, frequently interacted. total 38 proteins, calmodulin 2, Ras-related botulinum toxin substrate 1 (Rac1), PDGF-β, vimentin, found interact all six indicates a substantial number energetically underscoring complexity breadth strategies hijack host mechanisms. Further in vivo vitro validation is required understand implications interactions.

Language: Английский

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Neddylation and MASLD: From Pathophysiology to Therapy

Liver International, Journal Year: 2025, Volume and Issue: 45(5)

Published: April 11, 2025

ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly known as non‐alcoholic fatty (NAFLD), is intimately linked to the dysregulation of key transcription factors or enzymes involved in hepatic metabolism. Neddylation, a post‐translational modification, refers covalent attachment neuronal precursor cell‐expressed developmentally down‐regulated 8 (Nedd8) specific substrates and plays significant role regulating protein conformation, localisation activity. The connection between neddylation MASLD burgeoning area research that presently focus extensive study. In this review, we on latest advancements regarding various critical pathological stages MASLD. We summarise both confirmed potential evidence neddylation's involvement onset progression Additionally, review biological basis neddylation, its correlation with propose directions for basic translational field. Finally, emphasise therapeutic applications targeting MASLD, particularly designing pharmacological inhibitors have broad effects

Language: Английский

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MLN4924 alleviates autoimmune myocarditis by promoting Act1 degradation and blocking Act1-mediated mRNA stability

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 139, P. 112716 - 112716

Published: July 21, 2024

Prolonged exposure to interleukin-17A (IL-17A) can induce autoimmune myocarditis, and MLN4924, an inhibitor of NEDD8 activating enzyme (NAE), has been reported effectively suppress various inflammatory reactions. However, the effects MLN4924 in IL-17A-mediated inflammation associated with myocarditis remain uncertain.

Language: Английский

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Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Nov. 5, 2024

Neddylation, a type of protein post-translational modification that links the ubiquitin-like NEDD8 to substrate proteins, can be involved in various significant cellular processes and generate multiple biological effects. Currently, best-characterized substrates neddylation are Cullin family, which is core subunit Cullin-RING E3 ubiquitin ligase complex controls many important by promoting ubiquitination subsequent degradation key regulatory proteins. The normal or abnormal process central nervous system lead series occurrences functions development diseases, providing an attractive, reasonable, effective targeted therapeutic strategy. Therefore, this study reviews phenomenon summarizes corresponding substrates. Finally, we provide detailed description CNS diseases treatment methods may used regulate for related diseases.

Language: Английский

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Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 11, 2024

Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed investigate impact early neuronal differentiation human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent gene expression DNA methylation genes involved in neurodevelopmental processes or linked depression, such as BDNF , GDF11 CCL2 STC1 DDIT4 GAD2 . Single-cell RNA-sequencing analysis revealed distinct clusters cells, progenitors neuroblasts, where subtly influenced progenitor subtypes. Pseudotemporal showed enhanced differentiation. Our findings suggest that influences patterns associated with providing insights into its potential highlighting importance further research understand long-term consequences SSRI exposure.

Language: Английский

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Identification of COP9 Signalosome (CSN) Subunits and Antiviral Function Analysis of CSN5 in Shrimp

Published: Jan. 1, 2024

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) typically composing of eight subunits (CSN1-8) mediates the process deneddylation and deubiquitination. fifth subunit COP9 signalosome, CSN5, has special characteristics compared with other seven subunits, plays vital roles in activity diverse cellular processes. However, role CSN5 antiviral immunity is not clear. In this study, we identified 8 (CSN1−8) shrimp Marsupenaeus japonicus. CSN1-6 were existed all tested tissues, but CSN7-CSN8 detected hepatopancreas. After WSSV challenged, expression level Csn1 to Csn4, Csn6 Csn8 highly decreased, Csn5 was conspicuously increased challenged by white spot syndrome virus (WSSV). recombinantly expressed Escherichia coli its polyclonal antibody prepared. RNA protein levels WSSV. knockdown interference, replication obviously shrimp. When injected recombinant membrane penetrating peptide into shrimp, inhibited survival rate significantly improved control. We further analyzed antimicrobial peptides (AMPs) Csn5-RNAi results showed that several AMPs declined significantly. These indicate inhibits via regulation might be used aquaculture for disease

Language: Английский

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Identification of COP9 signalosome (CSN) subunits and antiviral function analysis of CSN5 in shrimp

Fish & Shellfish Immunology, Journal Year: 2024, Volume and Issue: 151, P. 109679 - 109679

Published: June 5, 2024

Language: Английский

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