Cell culture research in aging and Alzheimer's disease: The strategic use/reuse of untreated controls and savings people's tax dollars

Journal of Alzheimer s Disease Reports, Journal Year: 2025, Volume and Issue: 9

Published: Jan. 1, 2025

Cell culture is an essential tool in both fundamental and translational research, particularly for understanding complex diseases like Alzheimer's disease (AD). The use of cell lines provides the advantage genetic homogeneity, ensuring reproducible consistent results. This article explores application mammalian cultures to model AD, focusing on transfection cells with key genes associated replicate cellular environment AD. It explains various methods challenges related process. These models offer a robust platform investigating biology, molecular pathways, physiological processes, drug discovery efforts. A range assays, including RT-PCR, western blotting, ELISA, mitochondrial respiration, reactive oxygen species analysis, are employed assess impact modifications functions screen potential AD therapies. Researchers often design experiments multiple variables such as modifications, chemical treatments, or time points, paired positive negative controls. By using control group across all conditions under identical experimental conditions, researchers can minimize variability enhance data reproducibility. approach valuable where small differences significantly influence outcomes. Using shared ensures comparability experiments, saving resources by eliminating redundant tests. strategy not only streamlines research process but also improves reliability results, making it sensible, resource-efficient method that ultimately conserves public funding pursuit treatments.

Language: Английский

---

Experimental and theoretical studies on structural changes in the microtubule affinity-regulating kinase 4 (MARK4) protein induced by N-hetarenes: a new class of therapeutic candidates for Alzheimer’s disease

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: March 19, 2025

Introduction Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively affects the cognitive function and memory of affected person. Unfortunately, only handful effective prevention or treatment options are available today. Microtubule affinity-regulating kinase 4 (MARK4) serine/threonine protein plays critical role in regulating microtubule dynamics facilitating cell division. The dysregulated expression MARK4 has been associated with range diseases, including AD. Methods In this study, we synthesized series N -hetarenes via Pd(0)-catalyzed Suzuki-Miyaura cross coupling reaction. All compounds were characterized using multi-spectroscopic techniques evaluated for their activity against enzyme through ATPase inhibition assays. experimental data was further supported by computational quantum chemical calculations. We also computed drug-likeness, bioavailability, toxicity (ADME/T) profiles compounds. Results Six new 4-(6-(arylpyrimidin-4-yl)piperazine-1-carboximidamides 5−10 prepared good yields. assay conducted on these demonstrated IC 50 values micromolar (5.35 ± 0.22 to 16.53 1.71 μM). Among tested compounds, 4-(6-( p -tolyl)pyrimidin-4-yl)piperazine-1-carboximidamide ( 5 ; = 5.35 μM) 4-(6-(benzo[ b ]thiophen-2-yl)pyrimidin-4-yl)piperazine-1-carboximidamide 9 6.68 0.80 showed best activity. binding constant K ), as determined fluorescence quenching estimated be 1.5 0.51 × 10 M −1 1.14 0.26 . results molecular docking MD simulation studies (PDB: 5ES1) indicated able bind ATP pocket MARK4, leading its stabilization. Additionally, ADME/T analysis revealed high degree drug-likeness Conclusion 4-(6-(arylpyrimidin-4-yl)piperazine-1-carboximidamides) promising class developing next-generation anti-AD drugs. reported inhibited in-vitro at concentration targeting ATP-binding pocket. These findings provide valuable insights future drug design.

Language: Английский

---

Neurotrophic and Neurotoxic Effects of Aβ42 and Its Oligomers on Neuronal Survival: Revealed by Their Opposite Influence on the Potency of Extracellular BDNF

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4501 - 4501

Published: May 8, 2025

Brain-derived neurotrophic factor (BDNF) is critical for neuronal survival. Amyloid-β monomers (Aβ42M) and oligomers (Aβ42O) have trophic toxic effects on survival, respectively. Branched oligosaccharides (BOs) catechins (CAs) can specifically bind to Aβ42M/Aβ42O, influencing both effects. However, whether how Aβ42M/Aβ42O influences BDNF remains unknown. This study investigated the interaction between BDNF, of Aβ42M Aβ42O binding TrkB/p75 receptor their impact BDNF-supported cell roles BOs CAs in these processes. exhibited stronger affinity than BOs/CAs. increased viability by synergistically enhancing TrkB p75, whereas decreased inactivating/consuming thereby reducing its receptors. BDNF-Aβ42O appeared mutually neutralize/counteract each other’s biological effects; therefore, increasing levels might reduce Aβ42O’s neurotoxicity. By competitively targeting rather or receptors, enhanced These findings suggest that Aβ42M’s neurotrophicity was directly linked synergistic enhancement activity, neurotoxicity primarily due inactivation consumption BDNF. provided valuable insights developing BOs/CAs-based neuroprotective therapeutics nanomaterials against AD.

Language: Английский

---

Functional Relationships between L1CAM, LC3, ATG12, and Aβ

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10829 - 10829

Published: Oct. 9, 2024

Abnormal protein accumulations in the brain are linked to aging and pathogenesis of dementia various types, including Alzheimer’s disease. These can be reduced by cell indigenous mechanisms. Among these is autophagy, whereby proteins transferred lysosomes for degradation. Autophagic dysfunction hampers elimination pathogenic aggregations that contribute death. We had observed adhesion molecule L1 interacts with microtubule-associated 1 light-chain 3 (LC3), which needed autophagy substrate selection. increases survival an LC3-dependent manner via its extracellular LC3 interacting region (LIR). also Aβ reduces plaque load AD model mouse. Based on results, we investigated whether could aggregated clearance. here show autophagy-related 12 (ATG12) LIR domain, whereas interaction ubiquitin-binding p62/SQSTM1 does not depend LIR. Aβ, bound L1, carried autophagosome leading elimination. Showing mitophagy-related L1-70 fragment ubiquitinated, expect pathway contributes propose enhancing functions may therapy humans.

Language: Английский

---

Gut microbiota dysbiosis in patients with Alzheimer’s disease and correlation with multiple cognitive domains

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

Published: Nov. 27, 2024

Accumulating evidence suggested that Alzheimer's disease (AD) was associated with altered gut microbiota. However, the relationships between microbiota and specific cognitive domains of AD patients have yet been fully elucidated. The aim this study to explore microbial signatures global cognition in determine their predictive value as biomarkers.

Language: Английский

---