Novel targets for the treatment and prevention of Alzheimer's disease in the European population, inspiration from amyloid beta and tau protein DOI Creative Commons
Xifeng Wang, Huayu Yang,

Dengcheng Zhan

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(20), P. e39013 - e39013

Published: Oct. 1, 2024

Alzheimer's disease (AD) is a gradual neurodegenerative ailment that lacks any disease-modifying intervention. Our objective was to pinpoint pharmacological targets with focus on amyloid beta (Aβ) and tau treat prevent AD in the European population. A proteome-wide Mendelian randomization (MR) analysis carried out estimate associations between proteins cerebrospinal fluid (CSF) Aβ-42 phosphorylated Tau (p-Tau). We utilized colocalization MR investigate whether identified were associated risk of AD. Additionally, we expanded our investigation include non-AD phenotypes by conducting phenome-wide 1646 traits based FinnGen UK Biobank databases explore potential side effects. 11 genetically both CSF p-Tau levels. The predicted levels three proteins, GAL3ST2, POLR1C, BIN1, found be an increased high colocalization. In analysis, two biomarkers at least one disease, except for which not under threshold FDR <0.1. POLR1C most traits, all inhibited BIN1 protective. revealed level p-Tau. Among them, as therapeutic warrant further investigation.

Language: Английский

High Plasma Polyamine Levels Are Associated With an Increased Risk of Poststroke Cognitive Impairment: A Multicenter Prospective Study From CATIS DOI Creative Commons

Yu He,

Yiming Jia, Yi Liu

et al.

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Polyamines have been suggested to play pivotal roles in ischemic stroke and neurodegenerative disorders, but the associations of plasma polyamines with poststroke cognitive impairment (PSCI) remain unclear. We aimed prospectively investigate putrescine, spermidine, spermine PSCI among patients a multicenter cohort study. measured polyamine levels at baseline 619 from preplanned ancillary study CATIS (China Antihypertensive Trial Acute Ischemic Stroke). used Mini-Mental State Examination Montreal Cognitive Assessment evaluate function 3-month follow-up after stroke, was defined as score <27 or <25. According score, were positively associated PSCI. The adjusted odds ratios for highest versus lowest quartile 1.81 (95% CI, 1.09-3.00), 1.09-3.01), 1.92 1.15-3.20), respectively. In addition, putrescine (net reclassification improvement, 32.08%; P<0.001; integrated discrimination 1.62%; P=0.002), spermidine 25.29%; P=0.002; 1.22%; P=0.006), 16.54%; P=0.045; 1.36%; P=0.004) could significantly improve risk beyond established factors. There similar significant relationships when by score. Higher increased stroke. Our findings suggest that should be implicated pathophysiologic processes may potential intervention targets URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Language: Английский

Citations

0
Melatonin-governed growth and metabolome divergence: Circadian and stress responses in key plant species DOI Creative Commons
Soundaryaa Bargunam, Riyan Roy, Devika Shetty

et al.

Plant Physiology and Biochemistry, Journal Year: 2025, Volume and Issue: 221, P. 109635 - 109635

Published: Feb. 10, 2025

Melatonin, a versatile biomolecule, profoundly influences plant growth and resilience through its intricate regulation of metabolic pathways, circadian rhythms, cellular processes. The current study elucidates melatonin's concentration-dependent biphasic effects on dynamics in Arabidopsis thaliana Brassica nigra. While 50 μM melatonin optimized biomass accumulation root elongation, higher concentrations (100 μM) elicited stress responses, underscoring dual role as promoter modulator. Melatonin extended photosynthetic efficiency by modulating chlorophyll carotenoid synthesis diurnally, offering protection against photodamage. Divergent responses between the two species, driven species-specific reprogramming, were evident pigment biosynthesis antioxidant pathways. B. nigra displayed robust activation flavonoid phenylpropanoid cytokinin signaling, enhanced oxidative defenses, contrasting with A. thaliana, where suppressed precursors activation. Metabolomic analysis revealed orchestration hormonal crosstalk, involving auxins, gibberellins, jasmonates, to fine-tune adaptation. Stomatal cell wall fortification highlighted optimizing water-use structural under abiotic stress. Cytogenetic studies confirmed safeguarding genomic integrity, regulating chromatin remodeling, promoting DNA repair mechanisms, demonstrating adaptive strategies Moreover, influenced critical including polyamine biosynthesis, sulfur metabolism, nucleotide regulation, emphasizing multifaceted impact homeostasis. These findings position cornerstone molecule biotechnology, potential applications enhancing crop productivity fluctuating environmental conditions.

Language: Английский

Citations

0
A fluorescence-based assay for measuring aminopropyltransferase activity DOI
Pallavi Singh, Jae‐Yeon Choi, Choukri Ben Mamoun

et al.

Methods in enzymology on CD-ROM/Methods in enzymology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Endless Data for Drug Discovery Pipeline Validation for Free – Computational Chemistry’s Gift DOI
Stefan Ivanov

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Modern virtual high-throughput screening (vHTS) pipelines tend to be overmarketed and undervalidated, with no rigorous studies conclusively demonstrating that every one of their steps reliably adds increasing enrichment atop the baseline random hit rate. Moreover, what little benchmarking are available primarily focus on docking aspect pipelines, which is usually only beginning or near beginning, even there, authors use flawed data sets artificially inflate performance metrics. Herein, we present an alternative method pipeline validation set generation requires additional experimental work expenditure, yet offers negative superior both in terms quality quantity any used vHTS up now. By randomizing ligands across published structures generating structural isomers known binders, practically unlimited amounts can generated. Such positive points match closely molecular properties much more suitable for have far greater evidentiary value than current sets. Once such generated, they run through proposed pipeline, assessing at step. We stress importance using adequate definitively verifiably demonstrate utility a given tool workflow. Our goal help distinguish tools truly accelerate discovery lead optimization from ones promise do so but actually not, whereupon academia industry begin tackle many unaddressed medical needs 21st century.

Language: Английский

Citations

0
Novel targets for the treatment and prevention of Alzheimer's disease in the European population, inspiration from amyloid beta and tau protein DOI Creative Commons
Xifeng Wang, Huayu Yang,

Dengcheng Zhan

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(20), P. e39013 - e39013

Published: Oct. 1, 2024

Alzheimer's disease (AD) is a gradual neurodegenerative ailment that lacks any disease-modifying intervention. Our objective was to pinpoint pharmacological targets with focus on amyloid beta (Aβ) and tau treat prevent AD in the European population. A proteome-wide Mendelian randomization (MR) analysis carried out estimate associations between proteins cerebrospinal fluid (CSF) Aβ-42 phosphorylated Tau (p-Tau). We utilized colocalization MR investigate whether identified were associated risk of AD. Additionally, we expanded our investigation include non-AD phenotypes by conducting phenome-wide 1646 traits based FinnGen UK Biobank databases explore potential side effects. 11 genetically both CSF p-Tau levels. The predicted levels three proteins, GAL3ST2, POLR1C, BIN1, found be an increased high colocalization. In analysis, two biomarkers at least one disease, except for which not under threshold FDR <0.1. POLR1C most traits, all inhibited BIN1 protective. revealed level p-Tau. Among them, as therapeutic warrant further investigation.

Language: Английский

Citations

0