YAP in development and disease: Navigating the regulatory landscape from retina to brain

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116703 - 116703

Published: May 6, 2024

The distinctive role of Yes-associated protein (YAP) in the nervous system has attracted widespread attention. This comprehensive review strategically uses retina as a vantage point, embarking on an extensive exploration YAP's multifaceted impact from to brain development and pathology. Initially, we explore crucial roles YAP embryonic cerebral development. Our focus then shifts retinal development, examining detail regulatory influence pigment epithelium (RPE) progenitor cells (RPCs), its significant effects hierarchical structure functionality retina. We also investigate essential contributions maintaining homeostasis, highlighting precise regulation cell proliferation survival. In terms retinal-related diseases, epigenetic connections pathophysiological diabetic retinopathy (DR), glaucoma, proliferative vitreoretinopathy (PVR). Lastly, broaden our brain, emphasizing research paradigm "retina: window brain." Special is given emerging studies disorders such Alzheimer's disease (AD) Parkinson's (PD), underlining potential therapeutic value neurodegenerative neuroinflammation.

Language: Английский

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MST1 selective inhibitor Xmu-mp-1 ameliorates neuropathological changes in a rat model of sporadic Alzheimer’s Disease by modulating Hippo-Wnt signaling crosstalk

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(9-10), P. 1824 - 1851

Published: May 17, 2024

Language: Английский

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Buyang Huanwu decoction promotes angiogenesis after cerebral ischemia through modulating caveolin-1-mediated exosome MALAT1/YAP1/HIF-1α axis

Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155609 - 155609

Published: April 8, 2024

Language: Английский

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Degenerative Disease Diagnosis and Analysis Based on Tissue Specificity of DNA Methylation

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 452 - 452

Published: Jan. 7, 2025

The tissue specificity of DNA methylation refers to the significant differences in patterns different tissues. This regulates gene expression, thereby supporting specific functions each and maintenance normal physiological activities. Abnormal tissue-specific are closely related age-related diseases. abnormal pattern affects regulation which may lead changes cell function promote occurrence pathological conditions. By analyzing these patterns, key CpG sites for disease diagnosis can be effectively screened. main goal this paper is use characteristics associated with expression construct an model. First, we combined chi-square tests logistic regression identify disease-specific sites, laying foundation accurate medical diagnosis, verified biological relevance through enrichment analysis. Then used Transformer model fit realized automatic Our work proves that has potential diagnose diseases, scientific nature our proposed diagnostic method from a perspective.

Language: Английский

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Hippo-vgll3 signaling may contribute to sex differences in Atlantic salmon maturation age via contrasting adipose dynamics

Biology of Sex Differences, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 2, 2025

Abstract Background Sexual maturation in Atlantic salmon entails a transition energy utilization, regulated by genes and environmental stimuli sex-specific manner. Males require less energy, the form of adiposity, to mature typically younger than females. Maturation age is also influenced sex-dependent fashion vgll3 genotype ( vestigial-like 3 ), co-factor Hippo pathway. The underlying molecular processes age, their interplay with adiposity genotypes, remain unclear. Methods To elucidate mechanisms sex- genotype-specific differences, we investigated association early (E) late (L) alleles transcription > 330 involved regulation pathway sexual maturation, related signals brain, adipose, gonads. Results strongest effect was observed adipose for females brain males, highlighting expression differences genotype. Genes ovarian development showed increased vgll3*EE compared vgll3*LL Moreover, males exhibited reduced markers pre-adipocyte differentiation lipolysis yet enhanced adipocyte lipid storage. Brain gene further hormones lipids, as well tight junction assembly. Conclusions Overall, these patterns point towards greater storage slower utilization males. These results suggest Hippo-dependent may be important mediators sex salmon.

Language: Английский

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Plasma miRNA Biomarker Signatures in Parkinsonian Syndromes

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Language: Английский

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In vitro and in-vivo exploration of physostigmine analogues to understand the mechanistic crosstalk between Klotho and targets for epilepsy

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Background Epilepsy and seizures are characterized by neuronal hyperexcitability damage, influenced metabolic dysregulation, neuroinflammation, oxidative stress. Despite available treatments, many patients remain resistant to therapy, necessitating novel therapeutic strategies. Klotho, a neuroprotective, anti-inflammatory, antioxidative protein has emerged as potential modulator of epilepsy-related pathways. Objective This study investigates the physostigmine analogues in regulating Klotho expression its downstream targets epilepsy. Methods An integrative vitro vivo approach was employed PTZ-induced kindled mice. Behavioral assessments, including Morris Water Maze (MWM), Rota Rod, Black White Box, Tail Suspension tests were conducted. Biochemical analyses quantified serum glucose, lipid profiles, pro-inflammatory cytokines (TNF-α, FOXO1), apoptotic proteins (caspase-3). Quantitative real-time PCR (qRT-PCR) performed assess epilepsy-associated gene (STAT3, Bax, Bcl2). Results The synthesized exhibited varying inhibitory effects on transcriptional activators, with Compound C (1,8-bis(phenylsulfonyl)-1,8-dihydropyrrolo [2,3-b] indole) showing weakest inhibition (IC50 = 1.31 µM). In , demonstrated anticonvulsant (p < 0.05), neuroprotective (5 mg/kg, p 0.05, 10 0.01, 20 mg/kg 0.0001), antidepressant anti-inflammatory 0.05) seizure models, improving motor function 0.001), cognitive performance 0.01), reducing neuroinflammatory/metabolic markers while modulating STAT3 BAX Bcl2 expression. Conclusion 1,8-bis(phenylsulfonyl)-1,8-dihydropyrrolo indole epilepsy via modulation observed. Targeting metabolic, inflammatory, pathways presents promising strategy for management. Further research is required optimize clinical translation ensure long-term efficacy safety.

Language: Английский

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Therapeutic Effects of Baicalin on Diseases Related to Gut–Brain Axis Dysfunctions

Molecules, Journal Year: 2023, Volume and Issue: 28(18), P. 6501 - 6501

Published: Sept. 7, 2023

The gut–brain axis is an active area of research. Several representative diseases, including central nervous system disorders (Alzheimer’s disease, Parkinson’s and depression), metabolic (obesity-related diseases), intestinal (inflammatory bowel disease dysbiosis), are associated with the dysfunctional axis. Baicalin, a bioactive flavonoid extracted from Scutellaria baicalensis, reported to exert various pharmacological effects. This narrative review summarizes molecular mechanisms potential targets baicalin in Baicalin protects through anti-neuroinflammatory anti-neuronal apoptotic effects, suppresses obesity anti-inflammatory antioxidant alleviates regulatory effects on microorganisms short-chain fatty acid production. bioactivities mediated comprehensively role disorders, laying foundation for future research, although further confirmatory basic research required.

Language: Английский

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Single-cell RNA-sequencing analysis reveals α-syn induced astrocyte-neuron crosstalk-mediated neurotoxicity

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 139, P. 112676 - 112676

Published: July 24, 2024

Language: Английский

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Synaptic gene expression changes in frontotemporal dementia due to the MAPT 10+16 mutation

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 12, 2024

Abstract Mutations in the MAPT gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer’s disease, most common tauopathy, synapse loss is strongest pathological correlate of cognitive decline. Recently, PET imaging synaptic tracers revealed clinically relevant synapses primary tauopathies; however, molecular mechanisms leading to degeneration remain largely unknown. this study, we examined post-mortem brain tissue from people who died pathology (FTDtau) caused by intronic exon 10+16 mutation, which increases splice variants containing 10 resulting higher levels four microtubule binding domains. We used RNA sequencing and histopathology examine temporal cortex visual cortex, look for phenotypes compared age, sex, integrity matched participants without neurological disease (n=12 per group). Bulk reveals substantial downregulation expression associated function. Upregulated biological pathways human included those involved transcriptional regulation, DNA damage response, neuroinflammation. Histopathology confirmed increased accumulation FTDtau as well a presynaptic staining, region-specific colocalization phospho-tau cortex. Our data indicate that likely contributes pathogenesis mutation.

Language: Английский

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