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

The Journal of Infectious Diseases, Год журнала: 2024, Номер 230(3), С. e732 - e736

Опубликована: Фев. 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.

Язык: Английский

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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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The Relationships between Cerebrospinal Fluid Glial (CXCL12, CX3CL, YKL-40) and Synaptic Biomarkers (Ng, NPTXR) in Early Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(17), С. 13166 - 13166

Опубликована: Авг. 24, 2023

In addition to amyloid and tau pathology in the central nervous system (CNS), inflammatory processes synaptic dysfunction are highly important mechanisms involved development progression of dementia diseases. present study, we conducted a comparative analysis selected pro-inflammatory proteins CNS with reflecting damage core biomarkers mild cognitive impairment (MCI) early Alzheimer's disease (AD). To our knowledge, no studies have yet compared CXCL12 CX3CL1 markers disturbance cerebrospinal fluid (CSF) stages dementia. The quantitative assessment CSF patients MCI, AD, non-demented controls (CTRL) was performed using immunoassays (single- multiplex techniques). this increased concentration MCI AD correlated positively neurogranin (r = 0.74; p < 0.001, r 0.40; 0.020, respectively), ptau181 0.49; 0.040), YKL-40 0.47; 0.050) subjects. addition, elevated levels group were significantly associated mini-mental state examination score -0.32; 0.040). We found significant evidence support an association between neurogranin, already decline. Furthermore, findings indicate that might be useful marker for tract severity impairment.

Язык: Английский

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