Springer eBooks, Год журнала: 2024, Номер unknown, С. 255 - 268
Опубликована: Янв. 1, 2024
Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00570 - e00570
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
2
Cells, Год журнала: 2024, Номер 13(8), С. 719 - 719
Опубликована: Апрель 21, 2024
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss, imposing significant burden on affected individuals their families. Despite the recent promising progress in therapeutic approaches, more needs to be done understand intricate molecular mechanisms underlying development progression of AD. Growing evidence points epigenetic changes as playing pivotal role pathogenesis disease. The dynamic interplay between genetic environmental factors influences landscape AD, altering gene expression patterns associated with key pathological events pathogenesis. To this end, alterations not only impact genes implicated AD but also contribute dysregulation crucial cellular processes, including synaptic plasticity, neuroinflammation, oxidative stress. Understanding complex provides new avenues for interventions. This review comprehensively examines DNA methylation histone modifications context It aims deeper understanding facilitate targeted strategies.
Язык: Английский
Процитировано
12
Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18
Опубликована: Окт. 25, 2024
Neurovascular unit (NVU) inflammation via activation of glial cells and neuronal damage plays a critical role in neurodegenerative diseases. Though the exact mechanism disease pathogenesis is not understood, certain biomarkers provide valuable insight into pathogenesis, severity, progression therapeutic efficacy. These markers can be used to assess pathophysiological status brain including neurons, astrocytes, microglia, oligodendrocytes, specialized microvascular endothelial cells, pericytes, NVU, blood-brain barrier (BBB) disruption. Damage or derangements tight junction (TJ), adherens (AdJ), gap (GJ) components BBB lead increased permeability neuroinflammation various disorders disorders. Thus, neuroinflammatory evaluated blood, cerebrospinal fluid (CSF), tissues determine neurological progression, responsiveness. Chronic common age-related Alzheimer's (AD), Parkinson's (PD), dementia. Neurotrauma/traumatic injury (TBI) also leads acute chronic responses. The expression some may altered many years even decades before onset In this review, we discuss neuroinflammation, neurodegeneration associated with disorders, especially those neurovascular pathologies. CSF, tissues. Neurofilament light (NfL), ubiquitin C-terminal hydrolase-L1 (UCHL1), fibrillary acidic protein (GFAP), Ionized calcium-binding adaptor molecule 1 (Iba-1), transmembrane 119 (TMEM119), aquaporin, endothelin-1, platelet-derived growth factor receptor beta (PDGFRβ) are important markers. Recent BBB-on-a-chip modeling offers promising potential for providing an in-depth understanding neurotherapeutics. Integration these clinical practice could potentially enhance early diagnosis, monitor improve outcomes.
Язык: Английский
Процитировано
5
Immunity, Год журнала: 2025, Номер 58(1), С. 18 - 39
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Translational Neurodegeneration, Год журнала: 2025, Номер 14(1)
Опубликована: Янв. 16, 2025
Proteinopathies in neurology typically refer to pathological changes proteins associated with neurological diseases, such as the aggregation of amyloid β and Tau Alzheimer's disease, α-synuclein Parkinson's disease multiple system atrophy, TAR DNA-binding protein 43 amyotrophic lateral sclerosis frontotemporal dementia. Interestingly, these are also commonly found peripheral tissues, raising important questions about their roles disorders. Multiple studies have shown that peripherally derived not only travel brain through various routes, aggravating pathology, but contribute significantly dysfunction, highlighting crucial impact on diseases. Investigating how influence progression disorders could open new horizons for achieving early diagnosis treatment. This review summarizes distribution, transportation pathways, pathogenic mechanisms several neurodegenerative disease-related periphery, proposing targeting be a promising strategy preventing managing
Язык: Английский
Процитировано
0
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Янв. 31, 2025
Alzheimer's disease (AD) is a complex neurodegenerative disorder that currently lacks effective treatment options. This study aimed to identify potential therapeutic targets for the of AD using comprehensive bioinformatics methods and machine learning algorithms. By integrating differential gene expression analysis, weighted co-expression network Mfuzz clustering, single-cell RNA sequencing, algorithms including LASSO regression, SVM-RFE, random forest, five hub genes related AD, PLCB1, NDUFAB1, KRAS, ATP2A2, CALM3 were identified. in particular, exhibited highest diagnostic value showed significant correlation with Braak stages neuronal expression. Furthermore, Noscapine, PX-316, TAK-901 selected as drugs based on PLCB1. research provides reliable method discovery construction models, offering important insights directions future strategies drug development.
Язык: Английский
Процитировано
0
Extracellular Vesicles and Circulating Nucleic Acids, Год журнала: 2025, Номер 6(1), С. 87 - 111
Опубликована: Фев. 19, 2025
Aim: Microglial activation plays a pivotal role in the pathogenesis of retinal ganglion cell (RGC) degeneration resulting from optic nerve crush (ONC). Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have potential to prevent modulating microglial activation. In this study, we elucidated specific effects sEVs derived IFN-γ-primed MSCs on phenotypic transition microglia and associated pathways ONC mice. Methods: The mice model was established administered intravitreal injection with native (native sEVs) primed IFN-γ (IFNγ-sEVs). Their respective survival (RGCs) phenotypes were determined through visual function testing immunohistochemical staining. Combined mRNA seq microRNA techniques, mechanism modulation transformation IFNγ. Results: It demonstrated that IFNγ-sEVs exhibited superior protective against RGC loss reduced inflammatory responses retina compared sEVs. Both types promoted disease-associated (DAM) phenotype, while especially suppressed interferon-responsive (IRM) during RGCs degeneration. Subsequent miRNA sequencing suggested miR-423-5p , which most significant differential expression between two elevated IFNγ-sEVs, inhibited IRM ribosomal genes. Conclusion: These findings suggest IFN-γ-preconditioned may enhance neuroprotection suppressing secretion containing microRNAs
Язык: Английский
Процитировано
0
Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)
Опубликована: Март 3, 2025
Abstract Alzheimer’s disease (AD) is the most common neurodegenerative worldwide. Amyloid-β (Aβ) accumulation and neurofibrillary tangles are two key histological features resulting in progressive irreversible neuronal loss cognitive decline. The macrophages of central nervous system (CNS) belong to innate immune comprise parenchymal microglia CNS-associated (CAMs) at CNS interfaces (leptomeninges, perivascular space choroid plexus). Microglia CAMs have received attention as they may play a role onset progression e. g., by clearing amyloid beta through phagocytosis. Genome-wide association studies (GWAS) revealed that human express numerous risk genes for AD, further highlighting their potentially critical AD pathogenesis. tightly controlled environmental factors, such host microbiota. Notably, it was reported composition gut microbiota differed between patients healthy individuals. Hence, emerging analyzed impact bacteria different preclinical mouse models well clinical studies, enabling promising new therapeutic options.
Язык: Английский
Процитировано
0
Theranostics, Год журнала: 2025, Номер 15(8), С. 3401 - 3423
Опубликована: Фев. 24, 2025
Background: Abnormal activation of microglia occurs in the early stage Alzheimer's disease (AD) and leads to subsequent neuroinflammation major AD pathologies. Circular RNAs (circRNAs) are emerging as great potential therapeutic targets AD. However, extent circRNAs entwined underlying mechanism microglia-driven remain elusive. Methods: The circular RNA Dlg1 (circDlg1) was identified using circRNA microarray screening magnetic-isolated APP/PS1 mice. CircDlg1 expression mice patients validated by FISH. Flow cytometry immunostaining were conducted explore roles circDlg1 microglia. Adeno-associated virus 9 preparations for interfering with microglial microinjected into mouse lateral ventricle influences on response, Y-maze, novel object recognition Morris water maze tasks performed assess cognitive performance. pulldown assays, mass spectrometry analysis, immunoprecipitation, co-immunoprecipitation validate regulatory mechanisms circDlg1. Results: A observed elevated isolated from increased intracerebral patients. Microglia-specific knockdown remarkably ameliorated recruitment envelopment amyloid-β (Aβ), mitigated neuroinflammation, prevented decline Mechanistically, interfered interaction between phosphodiesterase 4b (PDE4B) Smurf2, an E3 ubiquitin ligase PDE4B. formed ternary complex protected PDE4B ubiquitination-dependent degradation via unique N-terminal targeting domain, thus consequently decreasing cAMP levels. We further confirmed that downregulation significantly activated PKA/CREB anti-inflammatory pathway protein levels Conclusion: microglia-upregulated tightly involves determining fate Microglial loss promotes protective response Aβ deposition relieves suggesting a strategy specifically
Язык: Английский
Процитировано
0
Natural Product Communications, Год журнала: 2025, Номер 20(3)
Опубликована: Март 1, 2025
Neuronal pyroptosis is one of the crucial pathogenesis neurodegenerative diseases, and signaling pathway mediated by inflammasome main pyroptosis. Neuroinflammation not only a common feature, but also an essential basis for diagnosis diseases. important pathological feature nervous system diseases such as Alzheimer's disease (AD), Parkinson's (PD). NLRP1 plays role in activating inducing inflammatory response, so development drugs targeting regulation has become reasonable research direction treatment By analyzing current progress which affects process neuronal related Chinese medicine, natural products were docked with targets to find higher activity. The target CB-Dock molecular docking platform. Molecular results showed that silibinin, crocin, hyperoside had excellent binding affinity, most promising potential active compounds AD regulating NLRP1. This paper discusses feasibility rationality medicine on future.
Язык: Английский
Процитировано
0