Current Sleep Medicine Reports, Journal Year: 2025, Volume and Issue: 11(1)
Published: Jan. 3, 2025
Language: Английский
Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)
Published: Feb. 21, 2025
Abstract Alzheimer’s disease (AD) poses a growing global health challenge as populations age. Recent research highlights the crucial role of peripheral immunity in AD pathogenesis. This review explores how blood-brain barrier disruption allows immune cells to infiltrate central nervous system (CNS), worsening neuroinflammation and progression. We examine recent findings on interactions between CNS-resident microglia, forming self-perpetuating inflammatory cycle leading neuronal dysfunction. Moreover, this emphasizes developments dysregulation factors from both periphery CNS, their impact With ongoing development new therapeutic strategies, underscores importance modulating CNS therapy.
Language: Английский
Citations
2
Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(12), P. 2052 - 2062
Published: Nov. 23, 2023
Language: Английский
Citations
39
Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)
Published: Feb. 28, 2023
Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of CNS pathogenesis Alzheimer's disease (AD). However, contribution nonparenchymal or brain-infiltrated to progression remains be demonstrated. Here, we show that monocyte-derived (MDC) invade brain parenchyma advanced stages AD continuum using transcriptional analysis immunohistochemical characterization post-mortem human hippocampus. Our findings demonstrated high proportion (60%) demented Braak V-VI individuals was associated with up-regulation genes rarely expressed by microglial abundant monocytes, among which stands membrane-bound scavenger receptor for haptoglobin/hemoglobin complexes Cd163. These Cd163-positive MDC invaded hippocampal parenchyma, acquired microglial-like morphology, were located close proximity blood vessels. Moreover, most interesting, these invading monocytes infiltrated nearby amyloid plaques contributing plaque-associated cell heterogeneity. aged-matched control pathology, no signs infiltration plaque invasion found. The previously reported degeneration/dysfunction hippocampus could key pathological factor inducing recruitment. data suggest clear association between endothelial activation turn may contribute damage barrier integrity. recruitment consequence rather than cause severity disease. Whether monocyte is beneficial detrimental pathology fully elucidated. open opportunity design targeted therapies, not only microglia but also peripheral population modulate provide better understanding immunological mechanisms underlying AD.
Language: Английский
Citations
33
Cells, Journal Year: 2023, Volume and Issue: 13(1), P. 54 - 54
Published: Dec. 26, 2023
This review analyzes the role of TNF-α and its increase in biological fluids mild cognitive impairment, Alzheimer’s disease (AD). The potential inhibition with pharmacological strategies paves way for preventing AD improving function people at risk dementia. We conducted a narrative to characterize evidence relation involvement possible therapeutic inhibition. Several studies report that patients RA systemic inflammatory diseases treated blocking agents reduce probability emerging dementia compared general population. Animal model also showed interesting results are discussed. An increasing amount basic scientific data clinical underscore importance processes subsequent glial activation pathogenesis AD. targeted therapy is biologically plausible approach cognition preservation further trials necessary investigate benefits populations developing
Language: Английский
Citations
32
EBioMedicine, Journal Year: 2023, Volume and Issue: 97, P. 104840 - 104840
Published: Oct. 18, 2023
SummaryJAK inhibitors impact multiple cytokine pathways simultaneously, enabling high efficacy in treating complex diseases such as cancers and immune-mediated disorders. However, their broad reach also poses safety concerns, which have fuelled a demand for increasingly selective JAK inhibitors.Deucravacitinib, first-in-class allosteric TYK2 inhibitor, represents remarkable advancement the field. Rather than competing at kinase domain catalytic sites classical JAK1-3 inhibitors, deucravacitinib targets regulatory pseudokinase of TYK2. It strikingly mirrors functional effect an evolutionary conserved naturally occurring variant, P1104A, known to protect against autoimmune yet provide sufficient TYK2-mediated signalling required prevent immune deficiency.The unprecedentedly selectivity efficacy-safety profile deucravacitinib, initially demonstrated psoriasis, combined with genetic support, promising outcomes early SLE clinical trials make this inhibitor ripe exploration other better, safe, efficacious treatments are urgently needed.
Language: Английский
Citations
31
Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)
Published: July 11, 2023
Abstract Background Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in pathogenesis of AD, but their crosstalk AD has not been studied. In this study, independent role interaction mitochondria-related genes cell infiltration were investigated using bioinformatics methods. Methods The datasets obtained from NCBI Gene Expression Omnibus (GEO), data mitochondrial was MitoCarta3.0 database. Subsequently, differential expression (DEGs) screening GSEA functional enrichment analysis performed. intersection DEGs related used to obtain MitoDEGs. MitoDEGs relevant determined by Least absolute shrinkage selection operator multiple support vector machine recursive feature elimination, as well protein–protein interactions (PPI) network random forest. 28 kinds cells analyzed ssGSEA, relationship between hub proportion levels verified models mice, OPA1 damage neuronal apoptosis investigated. Results functions pathways significantly enriched including response activation, IL1R pathway, metabolism, oxidative electron transport chain-oxphos system mitochondria. Hub closely based on PPI network, forest two learning algorithms. Five associated with neurological disorders identified biological function examination. found be correlated memory B cell, effector CD8 T activated dendritic natural killer type 17 helper Neutrophil, MDSC, plasmacytoid cell. These can also predict risk have good diagnostic efficacy. addition, mRNA BDH1, TRAP1, OPA1, DLD mice consistent results analysis, SPG7 showed a downward trend. Meanwhile, overexpression alleviated induced Aβ1-42. Conclusions potential identified. Their microenvironment may play crucial occurrence prognosis which provides new insight for studying exploring targets.
Language: Английский
Citations
30
Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(8), P. 4618 - 4640
Published: May 1, 2023
Language: Английский
Citations
24
Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(4), P. 289 - 302
Published: March 22, 2024
Selective vulnerability of specific brain regions and cell populations is a hallmark neurodegenerative disorders. Mechanisms selective involve neuronal heterogeneity, functional specializations, differential sensitivities to stressors pathogenic factors. In this review we discuss the growing body literature suggesting that, like neurons, astrocytes are heterogeneous specialized, respond integrate diverse inputs, induce effects on function. disease, undergo specific, context-dependent changes that promote different trajectories outcomes. We propose contribute through maladaptive transitions context-divergent phenotypes impair functions. Further studies multifaceted roles in disease may provide new therapeutic approaches enhance resilience against
Language: Английский
Citations
14
Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 193, P. 106461 - 106461
Published: March 2, 2024
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with pathological features of β-amyloid (Aβ) and hyperphosphorylated tau protein accumulation in the brain, often accompanied by cognitive decline. So far, our understanding extent role adaptive immune responses AD has been quite limited. T cells, as essential members system, exhibit quantitative functional abnormalities brains patients. Dysfunction blood-brain barrier (BBB) considered one factors leading to cell infiltration. Moreover, degree neuronal loss correlated quantity cells. We first describe differentiation subset functions peripheral cells patients provide an overview key findings related BBB dysfunction how infiltrate brain parenchyma through BBB. Furthermore, we emphasize risk associated AD, including Aβ, Tau protein, microglial apolipoprotein E (ApoE), neuroinflammation. discuss their regulation activation proliferation, well connection between neurodegeneration, Understanding innate response crucial for providing comprehensive personalized therapeutic strategies AD.
Language: Английский
Citations
13
Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 558 - 558
Published: May 30, 2024
Mood disorders and substance use disorder (SUD) are of immense medical social concern. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, it is only relatively recently that the role glia these attracted attention. Detailed understanding glial functions devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contributions neurotrophic factors, neuroinflammation, gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes, synantocytes) phenotypic manifestation or SUD emphasized. addition, knowledge potential development therapeutics touched upon.
Language: Английский
Citations
13