Recently updated role of Chitinase 3-like 1 on various cell types as a major infuencer of chronic inflammation

Опубликована: Фев. 28, 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 is component fungi, crustaceans, arthropods including insects and mites, parasites, completely absent from mammals, humans mice. In general, chitin-containing organisms produce protect body exogenous pathogen well hostile environments, it was thought similar effect in mammals. However, recent studies have revealed plays pro-inflammatory role by inducing anti-apoptotic activity epithelial cells macrophages. Under chronic inflammatory conditions such 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 will summarize under various disorders would like discuss potential roles those cell types.

Язык: Английский

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A Trisomy 21-linked Hematopoietic Gene Variant in Microglia Confers Resilience in Human iPSC Models of Alzheimer’s Disease

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 14, 2024

SUMMARY While challenging, identifying individuals displaying resilience to Alzheimer’s disease (AD) and understanding the underlying mechanism holds great promise for development of new therapeutic interventions effectively treat AD. Down syndrome (DS), or trisomy 21, is most common genetic cause Interestingly, some people with DS, despite developing AD neuropathology, show cognitive decline. Furthermore, DS are at an increased risk myeloid leukemia due somatic mutations in hematopoietic cells. Recent studies indicate that cells may lead neurodegeneration. Microglia, derived from lineages, play a central role etiology. We therefore hypothesize microglia carrying associated impart Using CRISPR-Cas9 gene editing, we introduce 21-linked hotspot CSF2RB A455D mutation into human pluripotent stem cell (hPSC) lines both healthy individuals. Employing hPSC-based vitro culture vivo chimeric mouse brain models, response pathological tau, suppresses microglial type-1 interferon signaling, independent 21 background. This reduces neuroinflammation enhances phagocytic autophagic functions, thereby ameliorating senescent dystrophic phenotypes microglia. Moreover, promotes unique subcluster tissue repair properties. Importantly, provide protection neuronal function, such as neurogenesis synaptic plasticity brains where largely repopulate hippocampus. When co-transplanted same brains, phagocytize replace wildtype following tau treatment. Our findings suggest hPSC-derived could be employed develop effective replacement therapy other age-related neurodegenerative diseases, even without need deplete endogenous diseased prior transplantation.

Язык: Английский

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Neuroinflammatory Proteins in Huntington’s Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11787 - 11787

Опубликована: Ноя. 2, 2024

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by CAG tract expansion in the huntingtin gene (

Язык: Английский

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Exploring SERPINA3 as a neuroinflammatory modulator in Alzheimer’s disease with sex and regional brain variations

Metabolic Brain Disease, Год журнала: 2025, Номер 40(1)

Опубликована: Янв. 4, 2025

Язык: Английский

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Characterization of Chitinase 3-like protein 1 spatiotemporal distribution in human post-traumatic brain contusions and other neuropathological scenarios

Journal of Neuropathology & Experimental Neurology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Abstract Chitinase 3-like protein 1 (CHI3L1) is emerging as a promising biomarker for assessing intracranial lesion burden and predicting prognosis in traumatic brain injury (TBI) patients. Following experimental TBI, Chi3l1 transcripts were detected reactive astrocytes located within the pericontusional cortex. However, cellular sources of CHI3L1 response to hemorrhagic contusions human remain unidentified. Hence, we examined comprehensive collection histologically defined acute subacute cerebral with various surgical intervals using immunohistochemistry, validated through double immunofluorescence markers such GFAP, NeuN, MBP, Iba-1, along Fluoro-Jade C histofluorescence staining. was found at meningeal interfaces, showing significant thickening subpial glial plate. Paradoxically, CHI3L1-positive identified neuroanatomical locations distant from foci, where numerous eosinophilic ischemic neurons also exhibited immunoreactivity. immunostaining extended into white matter tracts highlighted phagocytic or activated microglia forms after delayed decompressions. Given these findings, advise against astrogliosis marker due its expression multiple cell types, including astrocytes, neurons, oligodendrocytes, ependymocytes, leptomeningeal cells, microglia, blood vessels. This non-selective underscores potential elevation patterns biofluids reflect overall extent.

Язык: Английский

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