An In Vitro‐In Vivo Comparative Study Using Highly Sensitive Radioisotopic Assays to Assess the Predictive Power of Emerging Blood‐Brain Barrier Models DOI Open Access
Ahmed Refaat, Patrick B. Thomas,

Weisen Zhang

et al.

Small Methods, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Microfluidic BBB-on-a-chip models (μBBB) aim to recapitulate the organotypic features of human BBB with great potential model CNS diseases and advance therapeutics. Nevertheless, their predictive capacity for drug uptake into brain remains uncertain due limited evaluation only a small number drugs. Here, in vivo panel nine radiolabeled compounds is evaluated Swiss-outbred mice following single intravenously administered dose compared against results from microfluidic μBBB platform conventional Transwell model. Radioisotopic measurements are employed calculate brain-to-plasma concentration ratios (B/P) both vitro. The vitro-in correlation plots B/P revealed strong positive (r = 0.8081, R

Language: Английский

Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment DOI Creative Commons
Raymond J. Chan, Adam K. Walker, Janette Vardy

et al.

Supportive Care in Cancer, Journal Year: 2025, Volume and Issue: 33(4)

Published: March 6, 2025

This study reports on the results from our data-driven approach that identified perturbations in neuroactive ligand-receptor interaction and renin-angiotensin system (RAS) pathways oncology patients with without self-reported cancer-related cognitive impairment (CRCI). In a sample of receiving chemotherapy (n = 1343), Attentional Function Index (AFI) was used to assess CRCI. Patients were grouped into low (AFI score < 5) versus high > 7.5) levels function. Gene expression analyses done using RNA-seq 185) microarray 158) technologies. Pathway impact analysis evaluate for biological associated The combined pathway revealed RAS significantly perturbed between AFI scores. Findings this suggest addition inflammatory pathways, numerous mechanisms may contribute underlying development and/or persistence

Language: Английский

Citations

1
Emerging biophysical techniques for probing synaptic transmission in neurodegenerative disorders DOI
Mayur B. Kale, Nitu L. Wankhede, Ashok Kumar Bishoyi

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 565, P. 63 - 79

Published: Nov. 26, 2024

Language: Английский

Citations

6
Sulfonic acid functionalized β-amyloid peptide aggregation inhibitors and antioxidant agents for the treatment of Alzheimer's disease: Combining machine learning, computational, in vitro and in vivo approaches DOI
Vinit Raj, Chaitany Jayprakash Raorane,

Divya Shastri

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140142 - 140142

Published: Jan. 1, 2025

Language: Английский

Citations

0
Lycopodium alkaloids from Huperzia serrata and their cholinesterase inhibitory activities DOI
Shuai Jiang, Beibei Gao,

Yu‐Fei Ou

et al.

Phytochemistry, Journal Year: 2024, Volume and Issue: 223, P. 114114 - 114114

Published: April 30, 2024

Language: Английский

Citations

1
Tackling neurodegeneration in vitro with omics: a path towards new targets and drugs DOI Creative Commons
Caterina Carraro,

Jessica V. Montgomery,

Julien Klimmt

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: June 17, 2024

Drug discovery is a generally inefficient and capital-intensive process. For neurodegenerative diseases (NDDs), the development of novel therapeutics particularly urgent considering long list late-stage drug candidate failures. Although our knowledge on pathogenic mechanisms driving neurodegeneration growing, additional efforts are required to achieve better ultimately complete understanding pathophysiological underpinnings NDDs. Beyond etiology NDDs being heterogeneous multifactorial, this process further complicated by fact that current experimental models only partially recapitulate major phenotypes observed in humans. In such scenario, multi-omic approaches have potential accelerate identification new or repurposed drugs against multitude underlying One advantage for implementation these overarching tools able disentangle disease states model perturbations through comprehensive characterization distinct molecular layers (i.e., genome, transcriptome, proteome) up single-cell resolution. Because recent advances increasing their affordability scalability, use omics technologies drive nascent, but rapidly expanding neuroscience field. Combined with increasingly advanced vitro models, which benefited from introduction human iPSCs, multi-omics shaping paradigm NDDs, prediction screening. review, we discuss examples, main advantages open challenges targets therapies

Language: Английский

Citations

1
Quaternity method for integrated screening, separation, extraction optimization, and bioactivity evaluation of acetylcholinesterase inhibitors from Sophora flavescens Aiton DOI
Yutong Zhang, Yuchi Zhang, Sainan Li

et al.

Phytochemical Analysis, Journal Year: 2024, Volume and Issue: unknown

Published: July 3, 2024

Abstract Introduction Sophora flavescens Aiton (Fabaceae), a ubiquitous plant species in Asia, contains wide range of pharmacologically active compounds, such as flavonoids, with potential anti‐Alzheimer's disease (anti‐AD) effects. Objectives The objective the study is to develop quaternity method for screening, isolation, extraction optimization, and activity evaluation acetylcholinesterase (AChE)‐inhibiting compounds from S. realize high‐throughput screening substances traditional Chinese medicine provide experimental data development anti‐AD drugs. Methods With AChE target molecule, affinity ultrafiltration liquid chromatography‐mass spectrometry were applied screen inhibitors enzyme . Orthogonal array experiments combined multi‐objective Non‐Dominated Sorting Genetic Algorithm III was used first time optimize process extracting substances. Enzyme inhibition kinetics molecular docking studies performed verify effects compounds. Results Five AChE‐inhibiting identified: kushenol I, kurarinone, sophoraflavanone G, isokurarinone, E. These successfully separated at purities 72.88%, 98.55%, 96.86%, 96.74%, 95.84%, respectively, using n ‐hexane/ethyl acetate/methanol/water (4.0/5.0/4.0/5.0, v/v/v/v), (5.0/5.0/6.0/4.0, (4.9/5.1/5.7/4.3, v/v/v/v) mobile phase systems. revealed that E had best inhibitory effect. Conclusion This elucidates mechanism action five provides theoretical basis other therapeutic

Language: Английский

Citations

1
Natural compounds for Alzheimer's prevention and treatment: Integrating SELFormer-based computational screening with experimental validation DOI
Junyu Zhou,

Y. KIM,

Chen Li

et al.

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 185, P. 109523 - 109523

Published: Dec. 9, 2024

Language: Английский

Citations

1
Design, synthesis and evaluation of imidazo[1,2-a]pyrazin-8(7H)-one derivatives as acetylcholinesterase inhibitors and antioxidants DOI Creative Commons

Wen-Rong Du,

Ben-Ben Wei,

Xin-Yuan Guo

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 24, 2024

Abstract A series of 8-(piperazin-1-yl)imidazo[1,2-a]pyrazine derivatives were designed and synthesized as acetylcholinesterase inhibitors (AChEIs) antioxidants for the treatment Alzheimer's disease (AD). Moreover, biological evaluation results demonstrated that these compounds exhibited moderate inhibitory activities toward (AChE) radical scavenging activities. Among them, compound 14r was most potent AChE inhibitor with an IC50 value 0.47 µM activity against butyrylcholinesterase (BuChE) (IC50 = 11.02 µM). Meanwhile had best selectivity index (SI) values 23.45. Compound has better well compared to reference drug galantamine (AChE 5.01 µM, BuChE 18.46 SI 3.68). 14o antioxidant 89.33 which lower than ascorbic acid 25.70 µM) control drug. Furthermore, molecular docking studies indicated could simultaneously bind both catalytic active site peripheral anionic AChE, consistent mixed inhibition pattern shown by enzyme kinetic studies. The interaction’s stability 14r-AChE/BuChE also assessed using a conventional atomistic 100 ns dynamics simulation study, revealed conformational representative in cavity AChE. In addition, properties all predicted online through SwissADME, matched orally administered drugs. Based on properties, AChEI valuable further development.

Language: Английский

Citations

0
Design, synthesis and evaluation of imidazo[1,2-a]pyrazin-8(7H)-one derivatives as acetylcholinesterase inhibitors and antioxidants DOI

Wen-Rong Du,

Ben-Ben Wei,

Xin-Yuan Guo

et al.

Medicinal Chemistry Research, Journal Year: 2024, Volume and Issue: 33(10), P. 1938 - 1953

Published: Aug. 24, 2024

Language: Английский

Citations

0
An In Vitro‐In Vivo Comparative Study Using Highly Sensitive Radioisotopic Assays to Assess the Predictive Power of Emerging Blood‐Brain Barrier Models DOI Open Access
Ahmed Refaat, Patrick B. Thomas,

Weisen Zhang

et al.

Small Methods, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Microfluidic BBB-on-a-chip models (μBBB) aim to recapitulate the organotypic features of human BBB with great potential model CNS diseases and advance therapeutics. Nevertheless, their predictive capacity for drug uptake into brain remains uncertain due limited evaluation only a small number drugs. Here, in vivo panel nine radiolabeled compounds is evaluated Swiss-outbred mice following single intravenously administered dose compared against results from microfluidic μBBB platform conventional Transwell model. Radioisotopic measurements are employed calculate brain-to-plasma concentration ratios (B/P) both vitro. The vitro-in correlation plots B/P revealed strong positive (r = 0.8081, R

Language: Английский

Citations

0