Neurotherapeutics, Journal Year: 2022, Volume and Issue: 19(1), P. 186 - 208
Published: Jan. 1, 2022
Language: Английский
Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 77, P. 101619 - 101619
Published: April 5, 2022
Language: Английский
Citations
422
Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(1), P. 9 - 24
Published: March 2, 2022
Chitinase-3-like protein 1 (CHI3L1/YKL-40) has long been known as a biomarker for early detection of neuroinflammation and disease diagnosis Alzheimer's (AD). In the brain, CHI3L1 is primarily provided by astrocytes heralds reactive, neurotoxic state triggered inflammation other stress signals. However, how acts in or it contributes to AD relevant neurodegenerative conditions remains unknown. peripheral tissues, our group others have uncovered that master regulator wide range injury repair events, including innate immunity pathway resembles process governed microglia astrocytes. Based on assessment current knowledge regarding biology, we hypothesize functions signaling molecule mediating distinct neuroinflammatory responses brain cells misfunctions precipitate neurodegeneration. We also recommend future research directions validate such assertions better understanding mechanisms.
Language: Английский
Citations
84
Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(4), P. 555 - 570
Published: March 22, 2023
Language: Английский
Citations
58
Neuron, Journal Year: 2023, Volume and Issue: 111(15), P. 2383 - 2398.e7
Published: June 13, 2023
Language: Английский
Citations
48
Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(1), P. 1 - 18
Published: Jan. 4, 2024
Abstract Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 strongly upregulated by various inflammatory immunological diseases, including several cancers, Alzheimer’s disease, atherosclerosis. Several studies have shown can be considered as marker disease diagnosis, prognosis, activity, severity. In addition, the proinflammatory action may mediated via responses to cytokines, tumor necrosis factor-α, interleukin-1β, interleukin-6, interferon-γ. Therefore, contribute vast array diseases. However, its pathophysiological pharmacological roles in development diseases remain unclear. this article, we review recent findings regarding suggest therapeutic approaches target CHI3L1.
Language: Английский
Citations
36
Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 511 - 511
Published: March 14, 2024
Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s (PD), traumatic brain injury (TBI) Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions these pathogeneses is currently not clearly understood. These show dysregulated inflammatory responses, activation neurons, glial cells, neurovascular unit damage associated with excessive release proinflammatory cytokines, chemokines, neurotoxic mediators, infiltration peripheral immune cells into brain, as well entry mediators through damaged endothelial blood–brain barrier tight junction proteins. Activation leads to many molecules that cause neuroinflammation neurodegeneration. Gulf War Illness (GWI) myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) also dysfunctions. Currently, there no effective disease-modifying therapeutic options available for diseases. Human induced pluripotent stem cell (iPSC)-derived astrocytes, microglia, pericytes used models drug discovery. This review highlights certain recent trends in neuroinflammatory responses iPSC-derived applications
Language: Английский
Citations
34
Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(D1), P. D1151 - D1161
Published: Nov. 20, 2024
Abstract Identifying cell populations associated with risk variants is essential for uncovering cell-specific mechanisms that drive disease development and progression. Integrating genome-wide association studies (GWAS) single-cell RNA sequencing (scRNA-seq) has become an effective strategy detecting trait–cell relationships. The accumulation of trait-related single data led to urgent need its comprehensively processing. To address this, we developed sc2GWAS (https://bio.liclab.net/sc2GWAS/), which aims document large-scale GWAS regulatory pairs at resolution provide comprehensive annotations enrichment analyses these related pairs. current version curates a total 15 078 310 candidate from > 6 300 000 individual cells, offering valuable resource exploring complex relationships between traits cells. We applied strict quality control measures on both scRNA-seq data, ensuring the reliability accuracy datasets identification trait-relevant cells genes. In addition, provides ranked lists genes extensive (epi) genetic annotations, making it downstream analyses. demonstrate utility platform by investigating Alzheimer’s disease, where identified significant associations microglial APOE gene emerging as particularly significant. This facilitates detailed research into trait–gene interactions, anticipate will mechanisms.
Language: Английский
Citations
20
Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)
Published: Jan. 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.
Language: Английский
Citations
2
Neurology, Journal Year: 2021, Volume and Issue: 96(24)
Published: May 7, 2021
To perform a systematic review and meta-analysis to determine whether fluid imaging astrocyte biomarkers are altered in Alzheimer disease (AD).PubMed Web of Science databases were searched for articles reporting or AD. Pooled effect sizes determined with standardized mean differences (SMDs) using the Hedge G method random effects biomarker performance. Adapted questions from Quality Assessment Diagnostic Accuracy Studies applied quality assessment. A protocol this study has been previously registered PROSPERO (registration number: CRD42020192304).The initial search identified 1,425 articles. After exclusion criteria applied, 33 (a total 3,204 individuals) measuring levels glial fibrillary acidic protein (GFAP), S100B, chitinase-3-like 1 (YKL-40), aquaporin 4 blood CSF, as well monoamine oxidase-B indexed by PET 11C-deuterium-l-deprenyl, included. GFAP (SMD 0.94, 95% confidence interval [CI] 0.71-1.18) YKL-40 0.76, CI 0.63-0.89) CSF S100B 2.91, 1.01-4.8) found be significantly increased patients AD.Despite significant progress, applications AD remain their early days. This demonstrated that consistently supports further investigation inclusion clinical research framework observational interventional studies.
Language: Английский
Citations
95
Journal of Neurochemistry, Journal Year: 2021, Volume and Issue: 164(3), P. 309 - 324
Published: Dec. 21, 2021
Abstract Astrocytes are highly efficient homeostatic glial cells playing a crucial role in optimal brain functioning and homeostasis. respond to changes homoeostasis following central nervous system (CNS) injury/diseased state by specific defence mechanism called reactive astrogliosis. Recent studies have implicated placed astrogliosis the centre of pathophysiology Alzheimer's disease (AD) other neurodegenerative disorders. The AD biomarker field is evolving rapidly with new findings providing strong evidence which supports notion that an early event time course progression may precede pathological hallmarks AD. Clinical/translational vivo PET vitro postmortem imaging demonstrated ‘a first second wave’ distinct close‐loop relationships biomarkers at different stages disease. At end stages, astrocytes found be associated, or proximity, amyloid plaque tau deposits brains. Several PET‐tracers, being pipeline validated very fast pace for mapping visualising brain, will provide further invaluable mechanistic insights into non‐AD dementia pathologies. complementary roles microglia astrocyte activation progression, along clinical value fluid context existing biomarkers, latest avenue needs exploration.
Language: Английский
Citations
90