A systematic review and meta-analysis of tau phosphorylation in mouse models of familial Alzheimer’s disease DOI Creative Commons
Malamati Kourti, Athanasios Metaxas

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 17, 2023

Abstract Background Transgenic models of familial Alzheimer’s disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology. Here, we sought to evaluate levels phosphorylated tau (p-tau) protein, and explore potential age-related variations in hyperphosphorylation tau, mouse cerebral amyloidosis. Methods The PubMed Scopus databases were searched studies measuring soluble p-tau 5xFAD, APP swe / PSEN1 de9 , J20 APP23 mice. Data extracted analyzed using standardized procedures. Results For 5xFAD model, search yielded 36 eligible meta-analysis. Levels higher mice relative control, a difference that was evident both carboxy-terminal (CT) proline-rich (PR) domains tau. Age negatively moderated effects genotype on CT domain particularly hybrid mice, female preparations from cortex. 27 studies. Analysis showed transgenic vs. control animals, PR regions positively cortex A meta-analysis not performed models, due limited number these (<10 studies). Conclusions Although is hyperphosphorylated ageing are contingent upon model being examined. These observations emphasize importance tailoring selection appropriate stage when assessing relationship between Aβ suggest there optimal intervention points administration anti-amyloid anti-tau therapies.

Language: Английский

A systematic review and meta-analysis of tau phosphorylation in mouse models of familial Alzheimer's disease DOI Creative Commons
Malamati Kourti, Athanasios Metaxas

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 192, P. 106427 - 106427

Published: Feb. 1, 2024

Transgenic models of familial Alzheimer's disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology. In this meta-analysis, we sought to evaluate levels phosphorylated tau (p-tau) and explore potential age-related variations in hyperphosphorylation, within mouse AD. The PubMed Scopus databases were searched studies measuring soluble p-tau 5xFAD, APP

Language: Английский

Citations

6
Modulation of gut microbiota with probiotics as a strategy to counteract endogenous and exogenous neurotoxicity DOI
Anatoly V. Skalny, Michael Aschner, В. А. Гриценко

et al.

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 133 - 176

Published: Jan. 1, 2024

Language: Английский

Citations

6
Neuroprotective Mechanisms of Salidroside in Alzheimer’s Disease: A Systematic Review and Meta-analysis of Preclinical Studies DOI
Nan Zhang, Jianfei Nao, Xiaoyu Dong

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(46), P. 17597 - 17614

Published: Nov. 7, 2023

Alzheimer's disease (AD) is a neurodegenerative of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive dysfunction behavioral impairment. Salidroside (Sal) phenylpropanoid mainly isolated from Rhodiola species with various pharmacological effects. However, exact anti-AD mechanism Sal has not been clearly elucidated. This meta-analysis aims to investigate possible mechanisms which exerts its effects evaluating indicators biochemical characteristics. A total 20 studies were included, results showed treatment significantly improved behavior abnormalities AD animal models. With regard neurobiochemical indicators, could effectively increase antioxidant enzyme superoxide dismutase, decrease oxidative stress indicator malondialdehyde, inflammatory interleukin 1β, 6, tumor necrosis factor α. was effective reducing neuropathological such as amyloid-β levels number apoptotic cells. When relevant literature on rodent models combined Sal, therapeutic potential through multiple confirmed. further confirmation higher quality studies, larger sample sizes, more comprehensive outcome evaluations clinical trials needed future.

Language: Английский

Citations

10
NXP032 Improves Memory Impairment Through Suppression of Tauopathy in PS19 Mice and Attenuates Okadaic Acid-Induced Tauopathy in SH-SY5Y Cells DOI
Hyeyoon Eo,

Seong Hye Kim,

In Gyoung Ju

et al.

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 1, 2025

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
Shared early molecular mechanisms revealed in P301S and 5xFAD Alzheimer’s disease mouse models DOI Creative Commons

Huda Suloh,

Shashank Kumar Ojha,

Maryam Kartawy

et al.

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 26, 2025

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by early molecular events that influence progression. Still, mechanisms caused different mutations of AD are not understood. We have performed a multidisciplinary study to investigate and compare stages pathology in two transgenic mouse models: P301S 5xFAD. Using SNOTRAP-based mass spectrometry, we assessed changes S-nitrosylation, nitric oxide-mediated post-translational modification, proteins both models during their juvenile age. The increased levels 3-nitrotyrosine confirmed nitrosative stress mutant mice. Systems biology analysis revealed shared processes between models, particularly γ-aminobutyric acid (GABA)ergic glutamatergic neurotransmission processes. In model, identified 273 S-nitrosylated (SNOed) cortex, with 244 uniquely SNOed diseased 5xFAD 309 were identified. found altered expression glutamate/GABA-related markers cortex hippocampus models. Additionally, phosphorylation mTOR signaling components hyperactivation this pathway Conversely, mice showed no significant except for elevated ribosomal protein S6 cortex. Our findings key stages. These could serve as potential biomarkers therapeutic targets early-stage AD.

Language: Английский

Citations

0
Artemisiae Iwayomogii Herba mitigates excessive neuroinflammation and Aβ accumulation by regulating the pro-inflammatory response and autophagy-lysosomal pathway in microglia in 5xFAD mouse model of Alzheimer’s disease DOI
In Gyoung Ju, Seungmin Lee,

Hyeri Im

et al.

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

Published: Oct. 21, 2024

Language: Английский

Citations

3
Aerial part of Houttuynia cordata reverses memory impairment by regulating amyloid beta accumulation and neuroinflammation in Alzheimer's disease model DOI Open Access
In Gyoung Ju, Seungmin Lee, Jin Gyu Choi

et al.

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(7), P. 2854 - 2863

Published: Feb. 22, 2023

Alzheimer's disease (AD) is the most common neurodegenerative characterized by amyloid-β (Aβ) deposition, accompanied neuroinflammation and memory dysfunction. Houttuyniae Herba (aerial parts of Houttuynia cordata, also known as fish mint; HH), an herbal medicine traditionally used to treat fever, urinary disorders, pus, revealed protect neurons from Aβ toxicity regulate cholinergic dysfunction in AD models. In this study, we aimed investigate effects HH on excessive accumulation followed neuroinflammation, synaptic degeneration, impairment. Two-month-old 5xFAD transgenic mice were administered at 100 mg/kg for 4 months. We observed that treatment ameliorated impairment reduced deposits brains mice. directly inhibited aggregation vitro using Thioflavin T assay indirectly suppressed amyloidogenic pathway increasing alpha-secretase expression brain. addition, exerted antineuroinflammatory reducing glial activation p38 phosphorylation. Moreover, increased synaptophysin, a presynaptic marker protein. Overall, alleviates facilitating nonamyloidogenic inhibiting neuroinflammation. Therefore, suggest can be promising drug patients with requiring multifaceted improvement.

Language: Английский

Citations

8
Trichosanthis Semen Exerts Neuroprotective Effects in Alzheimer’s Disease Models by Inhibiting Amyloid-β Accumulation and Regulating the Akt and ERK Signaling Pathways DOI
In Gyoung Ju, Seung-Min Lee,

Seong Hye Kim

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 98(1), P. 119 - 131

Published: Feb. 13, 2024

Background: Alzheimer’s disease (AD), the most common form of dementia, is characterized by memory loss and abnormal accumulation senile plaques composed amyloid-β (Aβ) protein. Trichosanthis Semen (TS) a traditional herbal medicine used to treat phlegm-related conditions. While TS recognized for various bioactivities, including anti-neuroinflammatory effects, its ability attenuate AD remains unknown. Objective: To evaluate effects extract (TSE) on neuronal damage, Aβ accumulation, neuroinflammation in models. Methods: Thioflavin T western blot assays were assess aggregation vitro. was treated PC12 cells with neuroprotective effects. Memory functions histological brain features investigated TSE-treated 5×FAD transgenic mice intracerebroventricularly injected Aβ. Results: TSE disrupted increased viability phosphorylation both protein kinase B (Akt) extracellular signal-regulated (ERK) treatment also suppressed mice, protected subiculum medial septum, upregulated Akt/ERK hippocampus. Moreover, ameliorated decline glial overactivation observed mice. As assessing whether affect Aβ-induced neurotoxicity Aβ-injected improvement neuroinflammatory inhibition confirmed. Conclusions: aggregation, neurons against toxicity, neuroinflammation, suggesting that it can suppress development AD.

Language: Английский

Citations

1
A systematic review and meta-analysis of tau phosphorylation in mouse models of familial Alzheimer’s disease DOI Creative Commons
Malamati Kourti, Athanasios Metaxas

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 17, 2023

Abstract Background Transgenic models of familial Alzheimer’s disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology. Here, we sought to evaluate levels phosphorylated tau (p-tau) protein, and explore potential age-related variations in hyperphosphorylation tau, mouse cerebral amyloidosis. Methods The PubMed Scopus databases were searched studies measuring soluble p-tau 5xFAD, APP swe / PSEN1 de9 , J20 APP23 mice. Data extracted analyzed using standardized procedures. Results For 5xFAD model, search yielded 36 eligible meta-analysis. Levels higher mice relative control, a difference that was evident both carboxy-terminal (CT) proline-rich (PR) domains tau. Age negatively moderated effects genotype on CT domain particularly hybrid mice, female preparations from cortex. 27 studies. Analysis showed transgenic vs. control animals, PR regions positively cortex A meta-analysis not performed models, due limited number these (<10 studies). Conclusions Although is hyperphosphorylated ageing are contingent upon model being examined. These observations emphasize importance tailoring selection appropriate stage when assessing relationship between Aβ suggest there optimal intervention points administration anti-amyloid anti-tau therapies.

Language: Английский

Citations

0