Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice DOI Creative Commons
Elsa M. Reyes‐Reyes, Jessie Brown,

Michael Trial

и другие.

Experimental Brain Research, Год журнала: 2024, Номер 242(3), С. 543 - 557

Опубликована: Янв. 11, 2024

Abstract Apolipoprotein E ε4 allele (APOE4) is the predominant genetic risk factor for late-onset Alzheimer’s disease (AD). APOE4 mouse models have provided advances in understanding of pathogenesis, but unaccounted variables like rodent housing status may hinder translational outcomes. Non-sterile aspects food and bedding can be major sources changes microflora. Alterations intestinal microbial ecology cause mucosal barrier impairment increase pro-inflammatory signals. The present study examined role sterile non-sterile on redox indicators immune humanized- knock-in mice (hAPOe4). hAPOE4 were housed under conditions until 22 months age, followed by transfer a cohort to 2 months. At 24 redox/immunologic was evaluated flow cytometry/ELISA. females exhibited: (1) higher neuronal microglial oxygen radical production (2) lower CD68 + microglia (brain) CD8 T cells (periphery) compared sterile-housed mice. In contrast, males MHCII CD11b CD4 levels lipopolysaccharide-binding protein inflammatory cytokines periphery relative This demonstrated that vs. are associated with activation responses brain sex-dependent manner. Therefore, contribute variable outcomes both periphery.

Язык: Английский

Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies DOI Creative Commons
Jifa Zhang, Yinglu Zhang, Jiaxing Wang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Язык: Английский

Процитировано

184

Gut microbiota in Alzheimer’s disease: Understanding molecular pathways and potential therapeutic perspectives DOI

Simone Lista,

Antonio Munafò, Filippo Caraci

и другие.

Ageing Research Reviews, Год журнала: 2025, Номер 104, С. 102659 - 102659

Опубликована: Янв. 10, 2025

Язык: Английский

Процитировано

3

Can microbiota gut-brain axis reverse neurodegenerative disorders in human? DOI
Xingxing Yuan, Serge Yannick Ouédraogo,

Modou Lamin Jammeh

и другие.

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102664 - 102664

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1

The impact of physical exercise on neuroinflammation mechanism in Alzheimer’s disease DOI Creative Commons
Junhui Hu,

Baiqing Huang,

Kang Chen

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Авг. 21, 2024

Introduction Alzheimer’s disease (AD), a major cause of dementia globally, imposes significant societal and personal costs. This review explores the efficacy physical exercise as non-pharmacological intervention to mitigate impacts AD. Methods draws on recent studies that investigate effects neuroinflammation neuronal enhancement in individuals with Results Consistent alters neuroinflammatory pathways, enhances cognitive functions, bolsters brain health among AD patients. It favorably influences activation states microglia astrocytes, fortifies integrity blood-brain barrier, attenuates gut inflammation associated These changes are substantial improvements performance indicators. Discussion The findings underscore potential integrating into comprehensive management strategies. Emphasizing necessity for further research, this advocates refinement regimens maximize their enduring benefits decelerating progression

Язык: Английский

Процитировано

7

Novelties on Neuroinflammation in Alzheimer’s Disease–Focus on Gut and Oral Microbiota Involvement DOI Open Access
Cristina Popescu, Constantin Munteanu, Aurelian Anghelescu

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(20), С. 11272 - 11272

Опубликована: Окт. 19, 2024

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through microbiota–gut–brain axis, including Alzheimer’s disease (AD). This review aims to provide a comprehensive synthesis recent findings on involvement neuroinflammatory processes associated with AD, emphasizing novel insights therapeutic implications. reveals that dysbiosis AD patients’ is linked heightened peripheral central inflammatory responses. Specific bacterial taxa, such as Bacteroides Firmicutes gut, well Porphyromonas gingivalis cavity, are notably altered leading significant changes microglial activation cytokine production. Gut alterations increased intestinal permeability, facilitating translocation endotoxins like lipopolysaccharides (LPS) into bloodstream exacerbating by activating brain’s toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, short-chain fatty acids (SCFAs) amyloid peptides, can cross blood-brain barrier modulate While microbial amyloids may contribute amyloid-beta aggregation brain, certain SCFAs butyrate exhibit anti-inflammatory properties, suggesting potential avenue mitigate neuroinflammation. not only highlights critical pathology but also offers ray hope modulating could represent strategy for reducing slowing progression.

Язык: Английский

Процитировано

7

Dose-response relationship between nighttime sleep duration and intrinsic capacity declines among Chinese elderly: a cross-sectional study from CHARLS DOI Creative Commons
Bo Zhou, Ruijie Ma, Meng Wang

и другие.

BMC Public Health, Год журнала: 2025, Номер 25(1)

Опубликована: Март 17, 2025

Intrinsic capacity is a crucial indicator of adverse outcomes and has predictive value for diseases mortality. The objective this study to assess the association between nighttime sleep duration intrinsic in older Chinese adults. Data were collected from China Health Retirement Longitudinal Study (CHARLS) spanning years 2008–2020. Minimally sufficient adjustment was made confounding factors identified through Directed Acyclic Graphs (DAGs), multivariate logistic regression analysis conducted determine relationship capacity. Restricted cubic splines (RCS) used nonlinear population. Finally, subgroup interaction effect performed. Among 4994 adults, 3118 (62.4%) experienced decline After adjusting factors, associated with an increased risk (P < 0.001), exhibiting J-shaped pattern. For shows nonlinear, dose-response decline. Our provides important insights into health self-management

Язык: Английский

Процитировано

1

Advances in biomaterials for oral-maxillofacial bone regeneration: spotlight on periodontal and alveolar bone strategies DOI Creative Commons

N. Li,

Jinyu Wang,

Guangxia Feng

и другие.

Regenerative Biomaterials, Год журнала: 2024, Номер 11

Опубликована: Янв. 1, 2024

Abstract The intricate nature of oral-maxillofacial structure and function, coupled with the dynamic oral bacterial environment, presents formidable obstacles in addressing repair regeneration bone defects. Numerous characteristics should be noticed repair, such as irregular morphology defects, homeostasis between hosts microorganisms cavity complex periodontal structures that facilitate epithelial ingrowth. Therefore, necessitates restoration materials adhere to stringent specific demands. This review starts exploring these particular requirements by introducing bones then summarizes classifications current respect composition structure. Additionally, we discuss modifications including improving mechanical properties, optimizing surface topography pore adding bioactive components elements, compounds, cells their derivatives. Ultimately, organize a range potential optimization strategies future perspectives for enhancing materials, physical environment manipulation, microbial modulation, osteo-immune regulation, smart stimuli-responsive multifaceted approach poly-pathic treatment, hope providing some insights researchers this field. In summary, analyzes demands especially alveolar bone, concludes corresponding biomaterials aims inspire research pursuit more effective treatment outcomes.

Язык: Английский

Процитировано

6

Metabolic-associated steatotic liver disease and risk of Alzheimer’s disease: a real-world retrospective cohort study DOI Creative Commons
Jiaqi Zhang, Wenzhao Wang,

Xingyun Hou

и другие.

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Сен. 4, 2024

Alzheimer's Disease (AD) is increasingly recognized as being associated with metabolic disorders, including Metabolic Associated Steatotic Liver (MASLD). This study aimed to assess the relative risk of AD in individuals MASLD.

Язык: Английский

Процитировано

4

Iron Homeostasis Dysregulation, Oro-Gastrointestinal Microbial Inflammatory Factors, and Alzheimer’s Disease: A Narrative Review DOI Creative Commons
Agata Kuziak, Piotr B. Heczko,

Agata Pietrzyk

и другие.

Microorganisms, Год журнала: 2025, Номер 13(1), С. 122 - 122

Опубликована: Янв. 9, 2025

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder that profoundly impacts cognitive function and nervous system. Emerging evidence highlights pivotal roles iron homeostasis dysregulation microbial inflammatory factors in oral gut microbiome as potential contributors to pathogenesis AD. Iron disruption can result excessive intracellular accumulation, promoting generation reactive oxygen species (ROS) oxidative damage. Additionally, agents produced by pathogenic bacteria may enter body via two primary pathways: directly through or indirectly cavity, entering bloodstream reaching brain. This infiltration disrupts cellular homeostasis, induces neuroinflammation, exacerbates AD-related pathology. Addressing these mechanisms personalized treatment strategies target underlying causes AD could play critical role preventing its onset progression.

Язык: Английский

Процитировано

0

Porphyromonas gingivalis Induces Disturbance of Kynurenine Metabolism Through the Gut-Brain Axis: Implications for Alzheimer’s Disease DOI
He Zhu, Cheng Huang, Zhenhua Luo

и другие.

Journal of Dental Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Porphyromonas gingivalis is one of the major pathogens chronic periodontitis. P. can cause systemic inflammation, amyloid β protein deposition, and hyperphosphorylation tau protein, leading to Alzheimer’s disease (AD)–like lesions. oral infection causes gut microbiota alteration, barrier dysfunction, intestinal immune response inflammation. The microbiota-gut-brain axis has a potential role in pathogenesis AD. Whether affects AD-like lesions via gut-brain needs more study. In this study, orally administered induced alveolar resorption, impairment, Oral with microflora dysbiosis, imbalance tryptophan metabolism pathway microbiota, elevated levels 3-hydroxykynurenine sera hippocampi. key metabolite, 3-hydroxykynurenine, suppressed Bcl2 gene expression, neuronal apoptosis promoting vivo vitro. These findings suggest that induce AD through axis, providing new ideas for prevention treatment

Язык: Английский

Процитировано

0