Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells DOI

Annette Burkhart,

Steinunn Sara Helgudóttir,

Yahye A. Mahamed

et al.

Published: Oct. 3, 2024

Abstract Purpose The blood-brain barrier (BBB), formed by brain endothelial cells (BECs) ensures a stable microenvironment inside the regulating transport of blood-borne molecules to brain. However, neurodegenerative diseases are often accompanied neuroinflammation and BBB impairment mediated activated glial through their release proinflammatory cytokines. To study effects with respect BECs activation, we aimed develop an in vitro BBB model inflammation preactivating subsequently studying impact on BECs. Methods Primary mixed (MGCs) mainly containing astrocytes microglia were lipopolysaccharide (LPS)-stimulated, after which LPS-containing medium was removed. then co-cultured differentiated, unstimulated primary mouse in transwells meaning that under influence solely from cytokines other pro-inflammatory released cells. cytokine expression MGCs secretion culture quantitated LPS stimulation using qPCR Meso Scale analysis. inflammatory stimuli measured changes integrity, evaluated trans-endothelial electrical resistance (TEER), passive permeability tight junction proteins alterations, possibly altered adhesion molecules. indirect further compared directly stimulated LPS. Results significantly upregulated mRNA interleukin 6, 1β, tumor necrosis factor α increased several cytokines, e.g. IL-6, TNF-α, KC/ GRO (CXCL1) IL-12p70. Proving these influenced BECs, co-culturing pre-stimulated affected integrity similar direct leading lowering TEER permeability. Tight unaltered, but rearrangements proteins. Expression cell-adhesion LPS-prestimulated when Conclusion Activating denotes setting where transform into phenotype .

Language: Английский

Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer’s Disease and Other Neurodegenerative Diseases DOI Open Access
Yang Sun, Sadequl Islam, Makoto Michikawa

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1757 - 1757

Published: Feb. 1, 2024

Presenilin, a transmembrane protein primarily known for its role in Alzheimer’s disease (AD) as part of the γ-secretase complex, has garnered increased attention due to multifaceted functions various cellular processes. Recent investigations have unveiled plethora beyond amyloidogenic role. This review aims provide comprehensive overview presenilin’s diverse roles AD and other neurodegenerative disorders. It includes summary well-known substrates presenilin, such involvement amyloid precursor (APP) processing Notch signaling, along with functions. Additionally, it highlights newly discovered functions, trafficking function, regulation ferritin expression, apolipoprotein E (ApoE) secretion, interaction ApoE Aβ42-to-Aβ40-converting activity ACE. updated perspective underscores evolving landscape presenilin research, emphasizing broader impact established pathways. The incorporation these novel findings accentuates dynamic nature processes, further advancing our comprehension By synthesizing evidence from range studies, this sheds light on intricate web their implications health disease.

Language: Английский

Citations

11
Stress and the gut-brain axis: an inflammatory perspective DOI Creative Commons
Julia Morys, Andrzej Małecki, Marta Nowacka-Chmielewska

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: July 18, 2024

The gut-brain axis (GBA) plays a dominant role in maintaining homeostasis as well contributes to mental health maintenance. pathways that underpin the expand from macroscopic interactions with nervous system, molecular signals include microbial metabolites, tight junction protein expression, or cytokines released during inflammation. dysfunctional GBA has been repeatedly linked occurrence of anxiety- and depressive-like behaviors development. importance inflammatory aspects altered recently highlighted literature. Here we summarize current reports on signaling which involves immune response within intestinal blood-brain barrier (BBB). We also emphasize effect stress altering barriers' permeability, therapeutic potential microbiota restoration by probiotic administration transplantation, based latest animal studies. Most research performed various models showed an association between behaviors, dysbiosis gut microbiota, disruption permeability simultaneous changes BBB integrity. It could be postulated under conditions impaired communication across may therefore represent significant mechanism allowing affect brain functions.

Language: Английский

Citations

10
Protective Effects of Bifidobacterium Breve MCC1274 as a Novel Therapy for Alzheimer’s Disease DOI Open Access
Mona Abdelhamid, Scott Counts, Chunyu Zhou

et al.

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 558 - 558

Published: Jan. 31, 2025

Alzheimer’s disease (AD) is the most common form of dementia and characterized by memory impairment that significantly interferes with daily life. Therapeutic options for AD substantively modify progression remain a critical unmet need. In this regard, gut microbiota crucial in maintaining human health regulating metabolism immune responses, increasing evidence suggests probiotics, particularly beneficial bacteria, can enhance cognitive functions. Recent studies have highlighted positive effects Bifidobacterium breve MCC1274 (B. MCC1274) on individuals mild (MCI) schizophrenia. Additionally, oral supplementation B. has been shown to effectively prevent decline AppNL–G–F mice. relation pathology, found reduce amyloid-β (Aβ) accumulation tau phosphorylation both wild-type (WT) It also decreases microglial activation increases levels synaptic proteins. review, we examine AD, exploring potential mechanisms action how probiotic strain may aid preventing or treating disease. Furthermore, discuss broader implications improving overall host provide insights into future research directions promising therapy.

Language: Английский

Citations

1
Modulation of the Neuro–Cancer Connection by Metabolites of Gut Microbiota DOI Creative Commons
Alice Njolke Mafe, Dietrich Büsselberg

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 270 - 270

Published: Feb. 12, 2025

The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, cancer progression. Recent advances have accentuated significant role of microbiota metabolites in modulating systemic processes that influence both brain health tumorigenesis. This paper explores emerging concept metabolite-mediated modulation within connection, focusing on key such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, lipopolysaccharides (LPS). While microbiota's impact immune regulation, neuroinflammation, tumor development is well established, gaps remain grasping how specific contribute to neuro-cancer interactions. We discuss with potential implications for neurobiology cancer, indoles polyamines, which yet be extensively studied. Furthermore, we review preclinical clinical evidence linking dysbiosis, altered metabolite profiles, tumors, showcasing limitations research gaps, particularly human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal transplantation, probiotics, demonstrate promise but also indicate hurdles translating these findings therapies. concludes call standardized multi-omics approaches bi-directional frameworks integrating microbiome, neuroscience, oncology develop personalized therapeutic strategies patients.

Language: Английский

Citations

1
Optical coherence tomography angiography of the retina and choroid in systemic diseases DOI Creative Commons

Jacqueline Chua,

Bingyao Tan, Damon Wing Kee Wong

et al.

Progress in Retinal and Eye Research, Journal Year: 2024, Volume and Issue: 103, P. 101292 - 101292

Published: Aug. 30, 2024

Optical coherence tomography angiography (OCTA) has transformed ocular vascular imaging, revealing microvascular changes linked to various systemic diseases. This review explores its applications in diabetes, hypertension, cardiovascular diseases, and neurodegenerative While OCTA provides a valuable window into the body's microvasculature, interpreting findings can be complex. Additionally, challenges exist due relative non-specificity of where observed might not unique specific disease, variations between machines, lack standardized normative database for comparison, potential image artifacts. Despite these limitations, holds immense future. The highlights promising advancements like quantitative analysis images, integration artificial intelligence faster more accurate interpretation, multi-modal imaging combining with other techniques comprehensive characterization vasculature. Furthermore, OCTA's future role personalized medicine, enabling tailored treatment plans based on individual findings, community screening programs early disease detection, longitudinal studies tracking progression over time is also discussed. In conclusion, presents significant opportunity improve our understanding management Addressing current limitations pursuing exciting directions solidify as an indispensable tool diagnosis, monitoring progression, potentially guiding decisions across health conditions.

Language: Английский

Citations

7
The Glycocalyx: The Importance of Sugar Coating the Blood-Brain Barrier DOI Open Access
Candis Dancy, Kaitlyn E. Heintzelman, Moriah E. Katt

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8404 - 8404

Published: Aug. 1, 2024

The endothelial glycocalyx (GCX), located on the luminal surface of vascular cells, is composed glycoproteins, proteoglycans, and glycosaminoglycans. It plays a pivotal role in maintaining blood-brain barrier (BBB) integrity health within central nervous system (CNS), influencing critical processes such as blood flow regulation, inflammation modulation, permeability. While GCX ubiquitously expressed every cell body, at BBB highly specialized, with distinct composition glycans, physical structure, charge when compared to elsewhere body. There evidence that disrupted partially shed many diseases impact CNS. Despite this, has yet be major focus therapeutic targeting for CNS diseases. This review examines diverse model systems used cerebrovascular GCX-related research, emphasizing importance selecting appropriate models ensure clinical relevance translational potential. aims highlight disease how specifically may an effective approach brain specific therapeutics.

Language: Английский

Citations

4
Blood–Brain Barrier Disruption in Neuroimmunological Disease DOI Open Access
Fumitaka Shimizu, Masayuki Nakamori

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10625 - 10625

Published: Oct. 2, 2024

The blood–brain barrier (BBB) acts as a structural and functional for brain homeostasis. This review highlights the pathological contribution of BBB dysfunction to neuroimmunological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE), paraneoplastic neurological syndrome (PNS). transmigration massive lymphocytes across caused by activation cell adhesion molecules is involved in early phase MS, cortical associated with atrophy gray matter late MS. At onset NMOSD, increased permeability causes entry circulating AQP4 autoantibodies into central nervous system (CNS). Recent reports have shown importance glucose-regulated protein (GRP) BBB-reactive which induce antibody-mediated dysfunction. breakdown has also been observed MOGAD, NPSLE, AE anti-NMDAR antibodies. Our recent report demonstrated presence GRP78 patients MOGAD molecular mechanism responsible autoantibody-mediated impairment. Disruption may explain symptoms cerebellum development PNS, it induces pathogenic or CNS through autoimmunity against tumors periphery. were detected cerebellar degeneration Lambert–Eaton myasthenic syndrome, they ataxia anti-P/Q type voltage-gated calcium channel that therapies affecting are currently available disease-modifying diseases potential prevent damage.

Language: Английский

Citations

4
Multi-functional role of apolipoprotein E in neurodegenerative diseases DOI Creative Commons
Sadequl Islam, Arshad Ali Noorani, Yang Sun

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 29, 2025

Genetic diversity in the apolipoprotein E (ApoE) gene has been identified as major susceptibility genetic risk factor for sporadic Alzheimer’s disease (SAD). Specifically, ApoEε4 allele is a significant SAD, while ApoEε2 provides protection compared to more common ApoEε3 allele. This review discusses role of ApoE AD and other neurodegenerative disorders. ApoE, cholesterol transport protein, influences several pathways involved neurodegeneration, particularly AD. Beyond its established amyloid β -protein (Aβ) metabolism deposition, also impacts tau pathology, microglial response The aims provide an updated overview ApoE’s diverse roles, emphasizing involvement Aβ clearance through receptors. It covers influence diseases like Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington’s (HD), vascular dementia (VD), multiple (MS). New research highlights interaction between presenilin (PS), suggesting connections familial (FAD) SAD. explores protective effects mutations against ApoE4-induced tauopathy, neuroinflammation. insights from this comprehensive update could indeed lead new therapeutic strategies diseases.

Language: Английский

Citations

0
Hippocampal Apoptosis: Molecular Mechanisms Triggered by Toxic Cannabinoid Exposure: A Narrative Review DOI
Habibeh Mashayekhi‐Sardoo,

Mahdiyeh Hedayati-Moghadam,

Yousef Baghcheghi

et al.

NeuroToxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Transcriptome analysis reveals that the injection of mesenchymal stem cells remodels extracellular matrix and complement components of the brain through PI3K/AKT/FOXO1 signaling pathway in a neuroinflammation mouse model DOI Creative Commons

Zhihao Xu,

Keqin Liu,

Guoqing Zhang

et al.

Genomics, Journal Year: 2025, Volume and Issue: 117(3), P. 111033 - 111033

Published: March 22, 2025

Language: Английский

Citations

0