Associations among Angiotensin-Converting Enzyme, Neuroinflammation, and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in Non-Dementia Adults

Neurotoxicity Research, Journal Year: 2025, Volume and Issue: 43(2)

Published: April 1, 2025

Language: Английский

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In silico detection of dysregulated genes and molecular pathways in Alzheimer’s disease as basis for food restoring approach

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e19100 - e19100

Published: April 7, 2025

Forty-eight million people worldwide suffer from dementia, often associated with the growth of elderly population. There are also concerns about younger population, where increasing acute and chronic abuse alcohol neurotoxic substances may contribute to brain damage early onset dementia. Alzheimer’s disease (AD) accounts for 60% dementia cases most therapies used so far have been unsuccessful. Genetic, epigenetic vascular factors pathogenesis AD. Among mechanisms, modulation microRNA (miRs) plays an important role. To detect genes pathways involved in AD, we performed original bioinformatic analysis published dysregulated miRs using MIcroRNA ENrichment TURned NETwork (MIENTURNET) followed by Reactome tools. The interrogation these platforms allowed us discover common putative (by MIENTURNET) targeted which set altered tool). Our silico showed that β-catenin phosphorylation cascade Netrin-1 signalling, resulted as significant. Lastly, based on assumption food bioactive compounds (BC) modulate miRs, turn a literature search demonstrated some BC indeed able genes. Curcumin, osthole, puerarin, xanthoceraside, sulforaphane, salvianolic acid A, resveratrol andrographolide lead upregulation Wnt/β-catenin pathway. Choline, methionine, folate vitamin B6/B12 In conclusion, our identified their pathways, paving interesting new insights diagnosis potential therapeutic interventions.

Language: Английский

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Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: May 30, 2024

Clearance of amyloid-beta (Aβ) from the brain is impaired in both early-onset and late-onset Alzheimer’s disease (AD). Mechanisms for clearing cerebral Aβ include proteolytic degradation, antibody-mediated clearance, blood barrier cerebrospinal fluid efflux, glymphatic drainage, perivascular drainage. ATP-binding cassette (ABC) transporters are membrane efflux pumps driven by ATP hydrolysis. Their functions maintenance homeostasis removing toxic peptides compounds, transport bioactive molecules including cholesterol. Some ABC contribute to lowering Aβ. suggested transporter-mediated Aβ, addition exporting across barriers, apolipoprotein E lipidation, microglial activation, decreased amyloidogenic processing amyloid precursor protein, restricting entrance into brain. The transporter superfamily humans includes 49 proteins, eight which have been reduce levels. This review discusses experimental approaches increasing expression these transporters, clinical applications approaches, changes and/or activity AD transgenic mouse models AD, findings few trials examined effects patients with or mild cognitive impairment. possibility that therapeutic upregulation promote clearance may slow progression merits further consideration.

Language: Английский

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A Comprehensive Exploration of the Multifaceted Neuroprotective Role of Cannabinoids in Alzheimer’s Disease across a Decade of Research

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8630 - 8630

Published: Aug. 7, 2024

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests through dysregulation of brain function and subsequent loss bodily control, attributed to β-amyloid plaque deposition TAU protein hyperphosphorylation aggregation, leading neuronal death. Concurrently, similar cannabinoids the ones derived from Cannabis sativa are present in endocannabinoid system, acting receptors CB1R CB2R other related such as Trpv-1 GPR-55, being extensively investigated for AD therapy. Given limited efficacy adverse effects current available treatments, alternative approaches crucial. Therefore, this review aims identify effective natural synthetic elucidate their beneficial actions treatment. PubMed Scopus databases were queried (2014–2024) using keywords “Alzheimer’s disease” “cannabinoids”. The majority (Δ9-THC, CBD, AEA, etc.) (JWH-133, WIN55,212-2, CP55-940, included showed promise improving memory, cognition, behavioral symptoms, potentially via pathways involving antioxidant selective agonists (such BDNF/TrkB/Akt pathway) immunomodulatory (TLR4/NF-κB p65 pathway). Combining anticholinesterase properties with cannabinoid moiety may enhance therapeutic responses, addressing cholinergic deficits brains. Thus, positive outcomes vast studies discussed support further advancing clinical trials

Language: Английский

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Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease

Journal of Vascular Diseases, Journal Year: 2024, Volume and Issue: 3(4), P. 419 - 452

Published: Nov. 20, 2024

The microvessel neurovascular unit, with its brain endothelial cells (BEC) and blood–brain barrier remodeling, is important in the development of impaired cognition sporadic or late-onset Alzheimer’s disease (LOAD), which associated aging highly prevalent older populations (≥65 years age). It also linked vascular dementia contributions to cognitive impairment dementia, including cerebral amyloid angiopathy neurodegeneration. LOAD considered be number one cause globally; however, when considers role mixed (MD)—the combination both cascade hypothesis LOAD—it becomes apparent that MD cause. Microvessel BECs are first exposed peripheral neurotoxins from systemic circulation therefore at highest risk for early chronic injury. Therefore, these undergo injury, followed by excessive recurrent wound healing remodeling processes other age-related diseases such as cerebrocardiovascular disease, hypertension, type 2 diabetes mellitus, Parkinson’s disease. This narrative review explores intricate relationship between small vessel (SVD), neurodegeneration LOAD. discusses current understanding how dysfunction, disruption, pathology contribute pathogenesis highlights potential avenues therapeutic intervention.

Language: Английский

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Exploring the Synergistic Effects of Erinacines on Microglial Regulation and Alzheimer's Pathology Under Metabolic Stress

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(12)

Published: Dec. 1, 2024

ABSTRACT Background Hericium erinaceus mycelium and its constituents, erinacines A S, have shown neuroprotective effects in APP/PS1 transgenic mice; however, the precise mechanisms by which they modulate microglial phenotypes remain unclear. Our study is first to explore effect of on microglia morphology underlying using a novel primary mixed glia cell model advanced bioinformatic tools. Furthermore, we emphasize clinical relevance evaluating metabolically stressed mouse model, more accurately reflects complexities human Alzheimer's disease (AD), where metabolic syndrome common comorbidity. Methods Rat glial cultures were used simulate spectrum phenotypes, particularly transition from immature mature states. Microarray sequencing, along with Connectivity Map, ConsensusPathDB, Gene Set Enrichment Analysis, identified pathways influenced erinacines. The therapeutic efficacy was further evaluated mice. Results Erinacines significantly promoted development ramified, phenotype. Bioinformatics revealed potential modulation via histone deacetylase inhibition, actin filament dynamics, synaptic structure modification—pathways not previously linked AD. Importantly, lower fasting blood glucose insulin levels while reducing amyloid‐beta plaque burden, suppressing hyperactivated responses, enhancing neurogenesis Conclusion findings demonstrate dual action modulating phenotype providing neuroprotection that closely mimic disease. Additionally, this provides foundation for understanding erinacines, highlighting their promise as treatment approach Alzheimer's, cases complicated dysfunction.

Language: Английский

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Fatty acid amide hydrolase gene inactivation induces hetero‐cellular potentiation of microglial function in the 5xFAD mouse model of Alzheimer's disease

Glia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Abstract Neuroinflammation has recently emerged as a crucial factor in Alzheimer's disease (AD) etiopathogenesis. Microglial cells play an important function the inflammatory response; specifically, emergence of disease‐associated microglia (DAM) offered new insights into conflicting perspectives on detrimental or beneficial roles microglia. We previously showed that modulating endocannabinoid tone by fatty acid amide hydrolase (FAAH) inactivation renders effects amyloidosis context, paradoxically accompanied exacerbated neuroinflammatory response and enrichment DAM population. Here, we aim to elucidate role microglial FAAH‐lacking mice 5xFAD mouse model AD using RNA‐sequencing analysis, molecular determinations, morphological studies vivo multiphoton microscopy. displayed upregulated genes exhibited genetic profile. Conversely, linked were downregulated. Depleting PLX5622 revealed plaque‐associated FAAH‐deficient had more stable, ramified morphology increased Aβ uptake, leading reduced plaque growth compared control mice. Importantly, FAAH expression was negligible cells, thus suggesting for cellular interplay central nervous system. Our findings show Faah gene triggers hetero‐cellular enhancement paralleled response. Taken together, present data highlight potential therapeutic target AD.

Language: Английский

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The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Dec. 5, 2024

The pathophysiological role of Aβ

Language: Английский

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