The fibroblast growth factor system in cognitive disorders and dementia

Zhai, Wujianwen; Zhang, Tong; Jin, Yujing; Huang, Shijing; Xu, Manman; Pan, Juhua

doi:10.3389/fnins.2023.1136266

Cited by 4 publications

(2 citation statements)

References 186 publications

(196 reference statements)

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“…2J). Chronic neuroinflammation is a critical component of radiation induced neurotoxicity [4,5], and FGF-FGFR signalling has been suggested as an important regulator of neuroinflammation in several different cellular and pathological contexts [13], including multiple sclerosis (MS) [14], ischaemic stroke [15] and neurodegenerative diseases [16]. Specifically, FGF-1 and FGF-2 signalling has been implicated as a neuronal secreted factor that protects against neuroinflammation in animal models, likely by action on microglial migration [17,18].…”

Section: Irradiated Brain Tissue Harbours Disrupted Dna Methylation P...mentioning

confidence: 99%

The inflammatory micro-environment induced by targeted CNS radiotherapy is underpinned by disruption of DNA methylation

Millner,

Panday,

Xiao

et al. 2024

Preprint

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Although targeted radiotherapy (RT) is integral to the increasing survival of cancer patients, it has significant side-effects, the cellular and molecular mechanisms of which are not fully understood. During RT epigenetic changes occur in neoplastic tissue, but few studies have assessed these in non-neoplastic tissue and results are highly variable. Using bulk DNA methylation and RNA sequencing as well as spatial transcriptomics (ST) in a unique cohort of patient tissue samples, we show distinct differences in DNA methylation patterns in irradiated brain tissue, whilst ST characterisation identifies specific micro-environmental niches present after irradiation and highlights neuropeptides that could be propagating neuroinflammation. We also show that in a cerebral organoid (CO) model of early changes in neurons after irradiation there are similar DNA methylation alterations and disruption of the DNA methylation machinery, suggesting that early but persistent epigenetic dysregulation plays a role in neurotoxicity. We provide a link between radiotherapy induced neuroinflammation and disruption of DNA methylation for the first time and suggest possible driving mechanisms for this chronic neuroinflammation.

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Section: Irradiated Brain Tissue Harbours Disrupted Dna Methylation P...mentioning

confidence: 99%

The inflammatory micro-environment induced by targeted CNS radiotherapy is underpinned by disruption of DNA methylation

Millner,

Panday,

Xiao

et al. 2024

Preprint

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“…In HD, where selective vulnerability of certain neuronal populations is observed, FGFR signaling might in uence the survival of these neurons. FGFR signaling can have neuroprotective effects by promoting cell survival and inhibiting apoptosis [54,55]. In the context of HD, where neuronal death is a hallmark, FGFR's neuroprotective potential could be relevant.…”

Section: • Nrsf/restmentioning

confidence: 99%

Investigating the Gliogenic Genes and Signaling Pathways in the Pathogenesis of Huntington’s Disease: A Systematic Review

Shafi,

Raveena,

Yaqoob

et al. 2024

Preprint

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Background: The pathophysiology of Huntington's disease (HD), a neurodegenerative condition, is considered to also involve glial cells. Understanding the intricate interactions between neurons and glia can be accomplished by looking at gliogenic pathways and transcriptional dysregulation. Understanding glial involvement may result in novel medicines, biomarkers, and a thorough understanding of HD's molecular foundation, thereby altering patient outcomes and disease management. Methods: Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving Huntington’s disease, gliogenesis, gliogenic genes and signaling pathways, astrocytogenic genes. Results: This study reveals the complex interactions between gliogenic pathways and disease etiology. Key factors Pax6, Nkx6.1, Sox9, Sox4, and NFIX are impacted by transcriptional dysregulation, which may interfere with gliogenesis and cellular differentiation. TGF-beta, JAK-STAT, SHH, and NF-B dysregulated signaling pathways emphasize their part in astrocyte dysfunction and glial-neuronal interactions. GFAP, S100, and NF-B are implicated in neuroprotection and are also involved in HD pathogenesis. The intricate interplay of transcriptional factors and pathways complicates the mechanisms behind HD. Therapeutically, gliogenic pathway modulation, transcriptional balance restoration, and glial dysfunction targeting offer promising approaches to slow the course of HD. Even if there are still gaps, current research will improve our knowledge of gliogenic processes and of their possible implications in HD neurodegeneration. Conclusion: The investigation of gliogenic pathways and molecules in Huntington's disease (HD) reveals insights into potential glial dysfunction contributions. Alterations to signaling pathways (TGF-beta, JAK-STAT, SHH), astrocyte-related molecules (GFAP, S100, NF-B), and transcriptional dysregulation may all have an impact on how the disease develops. Complexity is added by transcription factors that affect cellular differentiation (HOPX, Sox9, Sox4, NFIX). The interaction between pathways emphasizes how complex HD pathogenesis is. Genetic and epigenetic alterations, stress reactions, and interactions between pathways all contribute to dysregulation. A growing understanding of gliogenesis and its possible implications in HD are provided in this study, opening up possibilities for therapeutic investigation and mitigating the effects of glial-driven HD.

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Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos

Xia,

Jian,

Rodrigue

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONWe conducted admixture mapping and fine‐mapping analyses to identify ancestry‐of‐origin loci influencing cognitive abilities.METHODSWe estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts.RESULTSWe identified nine local ancestry–associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13.DISCUSSIONOur study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry‐relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome‐wide association studies.Highlights We identified nine ancestry‐of‐origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non‐Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial‐mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.

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The fibroblast growth factor system in cognitive disorders and dementia

Cited by 4 publications

References 186 publications

The inflammatory micro-environment induced by targeted CNS radiotherapy is underpinned by disruption of DNA methylation

The inflammatory micro-environment induced by targeted CNS radiotherapy is underpinned by disruption of DNA methylation

Investigating the Gliogenic Genes and Signaling Pathways in the Pathogenesis of Huntington’s Disease: A Systematic Review

Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos

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