Comparative Study of Injected Alzheimer’s Disease Models in Rats: Insights from Experimental Research DOI Creative Commons

Hanane Doumar,

Hicham El Mostafi,

Aboubaker Elhessni

et al.

Pathophysiology, Journal Year: 2024, Volume and Issue: 31(4), P. 643 - 659

Published: Nov. 20, 2024

Background/Objectives: Alzheimer’s disease (AD) remains incurable, highlighting the need for new and diverse animal models to better understand its complex mechanisms. This study compares various injected of AD, focusing on main theories that explain disease; Methods: Female Wistar rats (10-months old) were administered intracebroventricularly by artificial cerebrospinal fluid (aCSF) (Control), beta amyloid Aβ1-42 (BA), okadaic acid (OKA), lipopolysaccharides (LPS), buthionine sulfoximine (BSO) or a mixture these different molecules (MLG). Cognitive performance was assessed one week month after stereotaxic surgery; Results: Our results, show only Aβ MLG induced persistence progressive deficits in working memory, recognition memory spatial rats. As hippocampus (HIP) prefrontal cortex (PFC) are particularly involved behavior, we analyzed long-term neuroadaptations brain subregions using spectrophotometric histological methods assess oxidative stress changes neuronal loss, respectively. We found behavioral impairments learning accompanied irreversible neurodegenerescence, HIP; Conclusions: provides promising data modeling AD order develop an effective therapeutic approach.

Language: Английский

Therapeutic modulation of mitochondrial dynamics by agmatine in neurodegenerative disorders DOI

Dhanshree Nibrad,

Amit Shiwal,

Manasi Tadas

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

2
Altered cognitive function in obese patients: relationship to gut flora DOI Creative Commons

Mengyuan Deng,

Fushan Tang, Zhaoqiong Zhu

et al.

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

2
Mitochondrial dysfunction in Alzheimer’s disease: a key frontier for future targeted therapies DOI Creative Commons
Shuguang Wang, Zuning Liao, Qiying Zhang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, accounting for approximately 70% of dementia cases worldwide. Patients gradually exhibit cognitive decline, such as memory loss, aphasia, and changes in personality behavior. Research has shown that mitochondrial dysfunction plays a critical role onset progression AD. Mitochondrial primarily leads to increased oxidative stress, imbalances dynamics, impaired mitophagy, genome abnormalities. These abnormalities are closely associated with amyloid-beta tau protein pathology, collectively accelerating process. This review summarizes mitochondria development AD, latest research progress, explores potential mitochondria-targeted therapeutic strategies Targeting mitochondria-related pathways may significantly improve quality life AD patients future.

Language: Английский

Citations

0
The potential link between the development of Alzheimer’s disease and osteoporosis DOI Creative Commons

Fariha Nasme,

Jyotirmaya Behera,

Prisha Tyagi

et al.

Biogerontology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 20, 2025

Language: Английский

Citations

0
Mitochondrial Alterations, Oxidative Stress, and Therapeutic Implications in Alzheimer’s Disease: A Narrative Review DOI Creative Commons

Erica Spina,

Riccardo Rocco Ferrari, Elisa Pellegrini

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 229 - 229

Published: Feb. 6, 2025

The relationship between aging, mitochondrial dysfunction, neurodegeneration, and the onset of Alzheimer’s disease (AD) is a complex area study. Aging primary risk factor for AD, it associated with decline in function. This dysfunction believed to contribute neurodegenerative processes observed AD. Neurodegeneration AD characterized by progressive loss synapses neurons, particularly regions brain involved memory cognition. It hypothesized that plays pivotal role disrupting cellular energy metabolism increasing production reactive oxygen species (ROS), which can damage components exacerbate neuronal loss. Despite extensive research, precise molecular pathways linking pathology are not fully understood. Various hypotheses have been proposed, including cascade hypothesis, suggests an early event pathogenesis triggers events leading neurodegeneration. With this narrative review, we aim summarize some specific issues literature on mitochondria their involvement onset, focus development therapeutical strategies targeting environment potential application treatment itself.

Language: Английский

Citations

0
Identification of biomarkers in Alzheimer’s disease and COVID-19 by bioinformatics combining single-cell data analysis and machine learning algorithms DOI Creative Commons
Juntu Li,

Linfeng Tao,

Yanyou Zhou

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0317915 - e0317915

Published: Feb. 18, 2025

Background Since its emergence in 2019, COVID-19 has become a global epidemic. Several studies have suggested link between Alzheimer’s disease (AD) and COVID-19. However, there is little research into the mechanisms underlying these phenomena. Therefore, we conducted this study to identify key genes associated with AD, evaluate their correlation immune cells characteristics metabolic pathways. Methods Transcriptome analyses were used common biomolecular markers of AD Differential expression analysis weighted gene co-expression network (WGCNA) performed on chip datasets (GSE213313, GSE5281, GSE63060) from patients both conditions. Gene ontology (GO) enrichment identified molecular mechanisms. The core using machine learning. Subsequently, evaluated relationship Finally, our findings validated through single-cell analysis. Results 484 differentially expressed (DEGs) by taking intersection black module, containing 132 genes, showed highest association two diseases according WGCNA. GO revealed that mainly affect inflammation, cytokines, immune-related functions, signaling pathways related metal ions. Additionally, learning approach eight genes. We links also found EIF3H oxidative phosphorylation. Conclusion This identifies shared pathways, alterations, changes potentially contributing pathogenesis AD.

Language: Английский

Citations

0
Opposite causal effects of type 2 diabetes and metformin on Alzheimer's disease DOI Creative Commons
Dongming Liu, Hongbao Cao, Ancha Baranova

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100129 - 100129

Published: March 1, 2025

Type 2 diabetes (T2D) is commonly co-morbid with Alzheimer's disease (AD). However, it remains unclear whether T2D itself or the antidiabetic drug metformin contributes to progression of AD. This study aimed investigate overall and independent effects use on risk Summary genome-wide association datasets were utilized for Mendelian randomization (MR) multivariable MR (MVMR) analyses, including ones (N = 455,017), 456,276), AD 453,733). Additionally, using proportional imbalance method, we analyzed AD-related adverse events in FDA Adverse Event Reporting System (FAERS) database (covering Q1 2004 Q2 2024). Our two-sample analysis indicated that not associated (OR: 1.03, CI: 0.99-1.08, P 0.128). while statistically significant, genetic signature exposure demonstrated a trend toward an increased 1.05, 1.00-1.09, 0.053). Interestingly, MVMR analysis, which evaluates T2D, found robust decrease 0.82, 0.68-0.98, 0.031), was higher 1.26, 1.06-1.50, 9.45E-3). In FAERS database, total 228,283 metformin-related event reports from 67,742 cases found. For as target event, signal reported 29 (ROR: 0.83, 95 % 0.58-1.19, 0.3126). reveals opposite causal These findings highlight importance assessing when prescribing patients T2D.

Language: Английский

Citations

0
Sequential Proteomic Analysis Reveals the Key APOE4‐Induced Pathological and Molecular Features at the Presymptomatic Stage in Alzheimer's Disease Mice DOI Creative Commons

Pengju Wei,

Kaihua Lin,

Xuhui Chen

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)

Published: March 1, 2025

Alzheimer's disease (AD) involves a prolonged presymptomatic or preclinical stage with subtle pathological changes. Apolipoprotein E4 (APOE4) is significant genetic risk factor for AD, yet its specific role at the not fully understood. This study aimed to elucidate cellular and molecular effects of APOE4 compared APOE3 on AD progression during stage. We generated 5xFAD mice carrying human their non-AD controls. Behavioral tests, immunostaining, quantitative proteomics phosphoproteomics, Golgi staining, Western blotting were conducted 3 10 months age, respectively. Cell culture experiments performed assess APOE4's direct impact neuronal mitochondrial function. significantly increased β-amyloid (Aβ) deposition microglial activation in stage, without aggravating blood-brain barrier disruption. Proteomic biochemical analysis revealed strong features synaptic degeneration dysfunction associated APOE4. Notably, promoted fusion mitophagy while inhibiting fission, leading impaired energy supply reactive oxygen species. Our findings indicate that accelerates pathologies by exacerbating Aβ deposition, neuroinflammation, degeneration. The highlights as critical mediator APOE4-induced progression, providing potential targets early intervention.

Language: Английский

Citations

0
Potential Roles of Natural Antioxidants in Modulating Neurodegenerative Disease Pathways DOI
Mega Obukohwo Oyovwi,

Ejime A. Chijiokwu,

Benneth Ben‐Azu

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Language: Английский

Citations

0
Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases DOI Creative Commons
Huan Xia, Zihao Wang, Xiaobei Wang

et al.

BMC Neurology, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 16, 2025

This study aims to investigate the causal relationship between Mitochondrial DNA (mtDNA) copy number and several common neurodegenerative diseases (NDs). We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS) as instrumental variables (IVs). After screening for relevance potential confounders, we estimated mtDNA NDs, including Alzheimer's disease (AD), Parkinson's (PD), Amyotrophic lateral sclerosis (ALS), Multiple (MS). Additionally, validated our findings GWAS on Longchamps et al., sourced Genetics Epidemiology Consortium UK Biobank (UKB) aging cohort. A of 395,718 UKB participants found no significant risk AD (OR = 0.956, P 0.708), PD 1.223, 0.179), ALS 0.972, 0.374), MS 0.932, 0.789). Similarly, reverse MR revealed genetic predictions NDs number: 0.987, 0.062), 0.997, 0.514), 0.974, 0.706), 1.003, 0.181). Although mitochondrial dysfunction is implicated in pathogenesis clear evidence supports role number. The likely mediated by more complex molecular regulatory mechanisms. Further research required elucidate these intricate interactions.

Language: Английский

Citations

0