Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 18, 2025

Abstract Chitinase-3-like-1 (CHI3L1) is an evolutionarily conserved protein involved in key biological processes, including tissue remodeling, angiogenesis, and neuroinflammation. It has emerged as a significant player various neurodegenerative diseases brain disorders. Elevated CHI3L1 levels have been observed neurological conditions such traumatic injury (TBI), Alzheimer’s disease (AD), Parkinson’s (PD), Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob (CJD), multiple (MS), Neuromyelitis optica (NMO), HIV-associated dementia (HAD), Cerebral ischemic stroke (CIS), tumors. This review explores the role of pathogenesis these disorders, with focus on its contributions to neuroinflammation, immune cell infiltration, neuronal degeneration. As regulator modulates microglia astrocyte activity, driving release proinflammatory cytokines that exacerbate progression. In addition pathology, promising biomarker for diagnosis monitoring cerebrospinal fluid (CSF) linked severity cognitive decline, particularly AD MS, highlighting potential clinical diagnostics. Furthermore, therapeutic strategies targeting CHI3L1, small-molecule inhibitors neutralizing antibodies, shown promise preclinical studies, demonstrating reduced amyloid plaque accumulation, improved survival. Despite potential, challenges remain developing selective safe CHI3L1-targeted therapies, ensuring effective delivery across blood–brain barrier mitigating off-target effects. addresses complexities highlights precision medicine, outlines future research directions aimed at unlocking full treating pathologies.

Язык: Английский

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Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson’s Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs

Brain Sciences, Год журнала: 2024, Номер 14(3), С. 238 - 238

Опубликована: Фев. 29, 2024

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson’s disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to unknown. To answer this question, mice received MPTP intraperitoneally construct subacute model and were then supplemented with orally 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, neurogenesis examined. In addition, intestinal inflammation, serum fecal short-chain fatty acids (SCFAs) analyses, assessed. We found treatment effectively inhibited reduction neurons substantia nigra pars compacta (SNpc) partially improved motor function mice. Additionally, markedly alleviated neuroinflammation striatum hippocampus promoted hippocampal neurogenesis. It also level colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations isovaleric acid levels, lower permeability. strongly neuroprotective agent therapy.

Язык: Английский

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

Cell Reports, Год журнала: 2024, Номер 43(5), С. 114226 - 114226

Опубликована: Май 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.

Язык: Английский

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Biomarkers for neuromyelitis optica: a visual analysis of emerging research trends

Neural Regeneration Research, Год журнала: 2024, Номер 19(12), С. 2735 - 2749

Опубликована: Апрель 1, 2024

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis. Over past 20 years, search for biomarkers neuromyelitis has been ongoing. Here, we used a bibliometric approach to analyze main research focus in field optica. Research this area consistently increasing, with China and United States leading way on number studies conducted. The Mayo Clinic highly reputable institution States, was identified as most authoritative field. Furthermore, Professor Wingerchuk expert Keyword analysis revealed terms "neuromyelitis optica" (261 times), "multiple sclerosis" (220 spectrum disorder" (132 "aquaporin 4" (99 "optical neuritis" (87 times) were frequently keywords literature related Comprehensive classical showed majority publications provide conclusive evidence supporting use aquaporin-4-IgG optica-IgG effectively diagnose differentiate emerged specific diagnostic biomarker disorder. Myelin oligodendrocyte glycoprotein-IgG myelin glycoprotein antibody-associated disease. Recent include cerebrospinal fluid immunological such glial fibrillary acidic protein, serum astrocyte damage like FAM19A5, albumin, gamma-aminobutyric acid. latest prospective clinical trials are exploring potential these biomarkers. Preliminary results indicate protein emerging promising candidate ultimate goal future identify non-invasive high sensitivity, specificity, safety accurate diagnosis

Язык: Английский

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Deterioration of neuroimmune homeostasis in Alzheimer’s Disease patients who survive a COVID-19 infection

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Авг. 17, 2024

Growing evidence has implicated systemic infection as a significant risk factor for the development and advancement of Alzheimer's disease (AD). With emergence SARS-CoV-2 (COVID-19) resultant pandemic, many individuals from same aging population vulnerable to AD suffered severe with potentially unidentified long-term consequences survivors. To study impact COVID-19 survival on brain's intrinsic immune system in also suffering AD, we profiled post-mortem brain tissue patients UF Neuromedicine Human Brain Tissue Bank diagnosis who survived (COVID-AD) contrasted our findings did not experience infection, including group donors passed away before arrival United States. We assessed disease-relevant protein pathology microglial astrocytic markers by quantitative immunohistochemistry supplemented these data whole gene expression analysis performed NanoString nCounter

Язык: Английский

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Inflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13437 - 13437

Опубликована: Дек. 15, 2024

Chitinase-3-like-1 (Chi3l1), also known as YKL-40 or BRP-39, is a highly conserved mammalian chitinase with chitin-binding ability but no enzymatic activity. Chi3l1 secreted by various cell types and induced several inflammatory cytokines. It can mediate series of biological processes, such proliferation, apoptosis, migration, differentiation, polarization. Accumulating evidence has verified that involved in diverse conditions; however, systematic comprehensive understanding the roles mechanisms almost all human body system-related diseases still lacking. The consists ten organ systems, which are combinations multiple organs perform one more physiological functions. Abnormalities these systems trigger environments, posing serious threats to quality life lifespan humans. Therefore, exploring novel reliable biomarkers for important, being parameter because its pathophysiological development diseases. Reportedly, plays an important role diagnosing determining disease activity/severity/prognosis related system inflammation disorders. Additionally, many studies have revealed influencing factors regulatory (e.g., ERK MAPK pathways) conditions, identifying potential therapeutic targets In this review, we comprehensively summarize underlying disorders respiratory, digestive, circulatory, nervous, urinary, endocrine, skeletal, muscular, reproductive provides Moreover, article summarizes strategies on basis mediated Chi3l1.

Язык: Английский

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Uncovering novel mechanisms of chitinase-3-like protein 1 in driving inflammation-associated cancers

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Июль 27, 2024

Abstract Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that induced and regulated by multiple factors during inflammation in enteritis, pneumonia, asthma, arthritis, other diseases. It associated with the deterioration of inflammatory environment tissues chronic caused microbial infection or autoimmune The expression CHI3L1 upregulated several malignant tumors, underscoring crucial role initiation progression cancer. While precise mechanism connecting cancer unclear, involvement involved inflammation, suggesting its as contributing factor to link between can aggravate DNA oxidative damage, induce cancerous phenotype, promote development tumor angiogenesis, inhibit immune cells, cell growth, invasion, migration. Furthermore, it participates metastasis binding transmembrane receptors mediate intracellular signal transduction. Based on current research CHI3L1, we explore introduce interact along signaling pathways may be triggered enhance tumorigenesis progression. In last section article, provide brief overview anti-inflammatory therapies target CHI3L1.

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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Single-cell analysis of CD14+CD16+ monocytes identifies a subpopulation with an enhanced migratory and inflammatory phenotype

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 20, 2025

Monocytes in the central nervous system (CNS) play a pivotal role surveillance and homeostasis, can exacerbate pathogenic processes during injury, infection, or inflammation. CD14+CD16+ monocytes exhibit diverse functions contribute to neuroinflammatory diseases, including HIV-associated neurocognitive impairment (HIV-NCI). Analysis of human matured vitro by single-cell RNA sequencing identified heterogenous population nine clusters. Ingenuity pathway analysis differentially expressed genes each cluster increased migratory inflammatory pathways for group clusters, which we termed Group 1 monocytes. monocytes, distinguished ALCAM, CD52, CD63, SDC2, exhibited gene expression signatures implicated CNS produced higher levels CXCL12, IL-1Ra, IL-6, IL-10, TNFα, ROS, preferentially transmigrated across blood-brain barrier model. Thus, cells within monocyte subset are likely be major contributors diseases.

Язык: Английский

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Neural Stem Cell Changes and Spatial Distribution of AQP4 Expression in a Fetal Goat Model of Obstructive Hydrocephalus

IBRO Neuroscience Reports, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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