Astrocyte-derived CHI3L1 signaling impairs neurogenesis and cognition in the demyelinated hippocampus

Cell Reports, Journal Year: 2024, Volume and Issue: 43(5), P. 114226 - 114226

Published: May 1, 2024

Cognitive dysfunction is a feature in multiple sclerosis (MS), chronic inflammatory demyelinating disorder. A notable aspect of MS brains hippocampal demyelination, which closely associated with cognitive decline. However, the mechanisms underlying this phenomenon remain unclear. Chitinase-3-like (CHI3L1), secreted by activated astrocytes, has been identified as biomarker for progression. Our study investigates CHI3L1's function within hippocampus and demonstrates correlation between CHI3L1 expression impairment patients MS. Activated astrocytes release reaction to induced adversely affects proliferation differentiation neural stem cells impairs dendritic growth, complexity, spine formation neurons. findings indicate that astrocytic deletion can mitigate neurogenic deficits dysfunction. We showed interacts CRTH2/receptor advanced glycation end (RAGE) attenuating β-catenin signaling. The reactivation signaling revitalize neurogenesis, holds promise therapy demyelination.

Language: Английский

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Magnetic transferrin nanoparticles (MTNs) assay as a novel isolation approach for exosomal biomarkers in neurological diseases

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

Brain-derived exosomes released into the blood are considered a liquid biopsy to investigate pathophysiological state, reflecting aberrant heterogeneous pathways of pathological progression brain in neurological diseases. provide promising prospects for diagnosis diseases, with exciting possibilities early and sensitive such However, capability traditional exosome isolation assays specifically isolate characterize brain-derived exosomal proteins by high-throughput proteomics clinical specimens from patients diseases cannot be assured. We report magnetic transferrin nanoparticles (MTNs) assay, which combined samples.The principle MTNs assay is ligand-receptor interaction through on receptor exosomes, electrostatic via positively charged negatively exosomes. In addition, simple rapid (< 35 min) does not require any large instrument. confirmed that accurately efficiently isolated serum samples humans neurodegenerative as dementia, Parkinson's disease (PD), multiple sclerosis (MS). Moreover, we 30 three distinct performed unbiased proteomic analysis explore pilot value protein profiles biomarkers.Using comparative statistical analysis, found 21 candidate biomarkers were significantly different among groups diseases.The convenient approach specific affordable extracellular vesicles body fluids minimally-invasive

Language: Английский

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Identification of cerebral spinal fluid protein biomarkers in Niemann-Pick disease, type C1

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Jan. 31, 2023

Niemann-Pick disease, type C1 (NPC1) is an ultrarare, recessive, lethal, lysosomal disease characterized by progressive cerebellar ataxia and cognitive impairment. Although the NPC1 phenotype heterogeneous with variable age of onset, classical a pediatric disorder. Currently there are no therapies approved FDA therapeutics trials for complicated rarity, heterogeneity, relatively slow rate neurological decline. Thus, identification relevant biomarkers necessary to provide tools that can support drug development efforts this devastating disease. Proximal extension assays (O-link® Explore 1536) were used compare cerebrospinal fluid (CSF) samples from individuals enrolled in natural history study non-NPC1 comparison samples. Relative expression levels 1467 proteins determined, candidate protein identified evaluating fold-change adjusted Kruskal-Wallis test p-values. Selected orthogonally confirmed using ELISA. To gain insight into progression severity we evaluated altered respect clinically phenotypic aspects: NPC Neurological Severity Score (NPC1 NSS), Annual Increment (ASIS) onset. This multiple CSF compared These included previously shown be elevated (NEFL, MAPT, CHIT1, CALB1) additional orthogonal (PARK7, CALB2/calretinin, CHI3L1/YKL-40, MIF, CCL18 ENO2). Correlations parameters demonstrated moderate negative (p = 0.0210, r -0.41) possible positive 0.0631, 0.33) correlation CALB2 onset ASIS, respectively. CHI3L1 showed 0.0183, 0.40) concurrent NSS. A strong 0.0016, -0.648) was observed between childhood/adolescent cases. also 0.0017, 0.61) ASIS. Our validated candidates further investigation larger cohort. analytes may prove useful as supportive data therapeutic trials. NCT00344331, NCT00001721, NCT02931682.

Language: Английский

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Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16149 - 16149

Published: Nov. 9, 2023

Chitinase-3-like protein 1 (CHI3L1), a chitinase-like family member, is secreted glycoprotein that mediates macrophage polarization, inflammation, apoptosis, angiogenesis, and carcinogenesis. Abnormal CHI3L1 expression has been associated with multiple metabolic neurological disorders, including diabetes, atherosclerosis, Alzheimer’s disease. Aberrant also reportedly tumor migration metastasis, as well contributions to immune escape, playing important roles in progression. However, the physiological pathophysiological of development neurodegenerative diseases cancer remain unclear. Understanding polarization relationship between macrophages crucial for disease Recent research uncovered complex mechanisms different diseases, highlighting its close association functional polarization. In this article, we review recent findings regarding various types summarize CHI3L1. Furthermore, article provides brief overview inhibitors employed inhibit disrupt interaction receptors. These endeavors highlight pivotal suggest therapeutic approaches targeting cancers.

Language: Английский

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Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis

Neurological Sciences, Journal Year: 2024, Volume and Issue: 45(6), P. 2489 - 2503

Published: Jan. 9, 2024

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there currently lack reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, CHI3L2 levels in cerebrospinal fluid (CSF) or blood their potential ALS patients. A systematic, comprehensive search was performed peer-reviewed English-language articles published before April 1, 2023, PubMed, Scopus, Embase, Cochrane Library, Web Science. After thorough screening, 13 primary were included, chitinases-related data extracted for systematic review meta-analysis. In patients, CSF CHIT1 significantly elevated compared controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 – 3.06; P < 0.001). patients other diseases (ONDS) 0.74; 0.22 1.27; 0.001) exhibited an even more substantial increase when ALS-mimicking (AMDS) 1.15; 0.35 1.94, Similarly, CHI3L1 higher HC 3.16; 1.26 5.06, ONDS 0.75; 0.32 1.19; = 0.017) pronounced AMDS 0.41 3.42; The chitinases showed significant increase, supporting role as biomarkers ALS.

Language: Английский

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Inhibition of Amyloid-β (Aβ)-Induced Cognitive Impairment and Neuroinflammation in CHI3L1 Knockout Mice through Downregulation of ERK-PTX3 Pathway

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5550 - 5550

Published: May 19, 2024

Several clinical studies reported that the elevated expression of Chitinase-3-like 1 (CHI3L1) was observed in patients suffering from a wide range diseases: cancer, metabolic, and neurological diseases. However, role CHI3L1 AD is still unclear. Our previous study demonstrated 2-({3-[2-(1-Cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}culfanyl)-

Language: Английский

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Multivariate GWAS of Alzheimer’s disease CSF biomarker profiles implies GRIN2D in synaptic functioning

Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)

Published: Oct. 4, 2023

Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF (β-amyloid, total/phosphorylated tau, NfL, YKL-40, neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, aimed to (1) identify common genetic variants associated with these profiles, (2) assess the role AD pathophysiology, (3) explore potential sex differences.

Language: Английский

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Recently Updated Role of Chitinase 3-like 1 on Various Cell Types as a Major Influencer of Chronic Inflammation

Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 678 - 678

Published: April 14, 2024

Chitinase 3-like 1 (also known as CHI3L1 or YKL-40) is a mammalian chitinase that has no enzymatic activity, but the ability to bind chitin, polymer of N-acetylglucosamine (GlcNAc). Chitin component fungi, crustaceans, arthropods including insects and mites, parasites, it completely absent from mammals, humans mice. In general, chitin-containing organisms produce chitinases, such CHI3L1, protect body exogenous pathogens well hostile environments, was thought had similar effect in mammals. However, recent studies have revealed plays pathophysiological role by inducing anti-apoptotic activity epithelial cells macrophages. Under chronic inflammatory conditions bowel disease obstructive pulmonary disease, many groups already confirmed expression significantly induced on apical side cells, activates downstream pathways involved inflammation carcinogenesis. this review article, we summarize under various disorders discuss potential roles those cell types.

Language: Английский

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Associations between saliva and plasma cytokines in cognitively normal, older adults

Aging Clinical and Experimental Research, Journal Year: 2022, Volume and Issue: 35(1), P. 117 - 126

Published: Nov. 1, 2022

Abstract Background Inflammatory responses play key roles in the development and progression of many pathological conditions, including neurodegenerative diseases. Accurate quantification inflammatory factors saliva would be highly advantageous, given its convenience non-invasive nature, especially elderly populations. Methods In this study, we measured levels 10 cytokines, pro-inflammatory factor, YKL-40, plasma samples from a cohort nondemented older adults ( n = 71; 62% female; 70.3 ± 6.4 years) using sensitive electrochemiluminescence-based immunoassays. Results We found that mean all cytokines were higher compared to strong sex differences observed for both population. Comparing each cytokine between two biofluids, interferon-gamma (IFNγ), interleukin (IL)-6 tumor necrosis factor-alpha (TNFα) blood significantly correlated with their respective saliva. further these additional saliva, IL-1β, IL-10, IL-8, IL12p70 IL-13. Conclusions These findings show markers are associated those circulation, suggesting shared mechanisms fluids. The suggest it might represent better peripheral fluid gauge processes. Finally, our robust several salivary could have important implications potential use as disease biomarkers related prevalence age-related conditions.

Language: Английский

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Exploring JC Polyomavirus Sequences and Human Gene Expression in Brain Tissue of Patients With Progressive Multifocal Leukoencephalopathy

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: 230(3), P. e732 - e736

Published: Feb. 14, 2024

Abstract Progressive multifocal leukoencephalopathy (PML) is a rare neurological condition associated with reactivation of dormant JC polyomavirus (JCPyV). In this study, we characterized gene expression and JCPyV rearrangements in PML brain tissue. Infection white matter astrocytes oligodendrocytes as well occasional cortex neurons was shown. harbored exclusively rearranged variants. Viral transcripts covered the whole genome on both strands. Strong differential human genes neuroinflammation, blood-brain barrier permeability, neurodegenerative diseases Pathway analysis revealed wide immune activation brain. The study provides novel insights into pathogenesis PML.

Language: Английский

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