High-Throughput Screening Platform for the Discovery of New Immunomodulator Molecules from Natural Product Extract Libraries

Palacio, José Pérez del; Díaz, Caridad; Cruz, Mercedes de la; Annang, Frederick; Martín, Jesús; Pérez-Victoria, Ignacio; González-Menéndez, Víctor; Pedro, Nuria de; Tormo, José R.; Algieri, Francesca; Rodríguez-Nogales, Alba; Reyes, Fernando; Genilloud, Olga; Vicente, Francisca; Gálvez, Júlio

doi:10.1177/1087057116635517

Cited by 19 publications

(27 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three-dimensional culture techniques based on the generation of organoids derived from induced pluripotent stem cells, developed in recent years, may be of great value in advancing the generation of biohybrid devices to evaluate new therapeutic alternatives, furthering the understanding of molecular transport mechanisms, and providing an individualized model to simulate conditions close to those that could be found in actual patient tissue [ 53 , 54 ]. High-throughput screening (HTS) techniques can be a complementary tool, as well as assays based on cells and biochemical techniques such as those described by Aldewachi et al [ 55 ] in 2021 and by Pérez del Palacio et al [ 56 ] in 2016, which are necessary and fundamental for analyzing the potential of possible drugs.…”

Section: Discussionmentioning

confidence: 99%

Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System

Gómez‐Pinedo¹,

García-Ávila²,

Gallego-Villarejo³

et al. 2021

IJMS

View full text Add to dashboard Cite

Introduction: AQP4 (aquaporin-4)–immunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination capacity in neuromyelitis optica is yet to be determined, as is the role of AQP4–IgG in cell differentiation. Material and Methods: We included three groups—a group of patients with AQP4–IgG-positive neuromyelitis optica, a healthy group, and a sham group. We analyzed differentiation capacity in cultures of neurospheres from the subventricular zone of mice by adding serum at two different times: early and advanced stages of differentiation. We also analyzed differentiation into different cell lines. Results and Conclusions: The effect of sera from patients with NMOSD on precursor cells differs according to the degree of differentiation, and probably affects oligodendrocyte progenitor cells from NG2 cells to a lesser extent than cells from the subventricular zone; however, the resulting oligodendrocytes may be compromised in terms of maturation and possibly limited in their ability to generate myelin. Furthermore, these cells decrease in number with age. It is very unlikely that the use of drugs favoring the migration and differentiation of oligodendrocyte progenitor cells in multiple sclerosis would be effective in the context of neuromyelitis optica, but cell therapy with oligodendrocyte progenitor cells seems to be a potential alternative.

show abstract

Section: Discussionmentioning

confidence: 99%

Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System

Gómez‐Pinedo¹,

García-Ávila²,

Gallego-Villarejo³

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Mammalian and/or human cell-based natural products HTS has been employed in a wide range of disease areas and cellular phenomena. A few examples include immunomodulation, 71,72 nuclear export, 73 and metabolomics, 74 and disease areas including diabetes 75 and cystic brosis 76 among many active target areas. 77 Cell-based assays for natural product discovery have been particularly plentiful in cancer research.…”

Section: Cell-based Hts For Natural Product Discoverymentioning

confidence: 99%

Creating and screening natural product libraries

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Particularly, several approaches have been proposed for high-throughput screening (HTS) in vitro: (i) cell-based and biochemical assays that allow getting data on cell proliferation, differentiation, migration, cell-to-cell interactions, or signal transduction and metabolic status, respectively; (ii) application of omics technologies (genomics, transcriptomics, proteomics, metabolomics, etc.) even in the single-cell format if possible; (iii) application of real-time protocols and development of models with the integrated sensors for analyzing cell behavior and BBB permeability; iv) combining in vitro modeling with in silico modeling to provide informative and predictive protocols [ 145 , 146 , 147 ]. Thus, selection of a BBB in vitro model for HTS is mainly based on the parameters that should be taken for consideration: i.e., evaluating the wide spectrum of xenobiotics for their transport across the BBB might require simple 2D transwell systems, but cell-to-cell interactions and signal transduction pathways, i.e., mitochondria-driven mechanisms in BMECs required for barrier function, could be reproduced with high reliability in 3D models or in ones allowing for real-time analysis.…”

Section: Application Of In Vitro Nvu/bbb Models For Studying Mitochondria-related Changes In Cell Metabolism: Current Trends and Challengmentioning

confidence: 99%

Blood–Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration

Салмина

Kharitonova

Gorina

et al. 2021

IJMS

View full text Add to dashboard Cite

Pathophysiology of chronic neurodegeneration is mainly based on complex mechanisms related to aberrant signal transduction, excitation/inhibition imbalance, excitotoxicity, synaptic dysfunction, oxidative stress, proteotoxicity and protein misfolding, local insulin resistance and metabolic dysfunction, excessive cell death, development of glia-supported neuroinflammation, and failure of neurogenesis. These mechanisms tightly associate with dramatic alterations in the structure and activity of the neurovascular unit (NVU) and the blood–brain barrier (BBB). NVU is an ensemble of brain cells (brain microvessel endothelial cells (BMECs), astrocytes, pericytes, neurons, and microglia) serving for the adjustment of cell-to-cell interactions, metabolic coupling, local microcirculation, and neuronal excitability to the actual needs of the brain. The part of the NVU known as a BBB controls selective access of endogenous and exogenous molecules to the brain tissue and efflux of metabolites to the blood, thereby providing maintenance of brain chemical homeostasis critical for efficient signal transduction and brain plasticity. In Alzheimer’s disease, mitochondria are the target organelles for amyloid-induced neurodegeneration and alterations in NVU metabolic coupling or BBB breakdown. In this review we discuss understandings on mitochondria-driven NVU and BBB dysfunction, and how it might be studied in current and prospective NVU/BBB in vitro models for finding new approaches for the efficient pharmacotherapy of Alzheimer’s disease.

show abstract

High-Throughput Screening Platform for the Discovery of New Immunomodulator Molecules from Natural Product Extract Libraries

Cited by 19 publications

References 31 publications

Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System

Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System

Creating and screening natural product libraries

Blood–Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration

Contact Info

Product

Resources

About