Establishment of a novel cellular model for Alzheimer's disease in vitro studies

Theodor Bilharz Research Institute

Bibliographic Information

Authors: El-Araby R.E.; Wasif K.; Johnson R.; Tu Q.; Aboushousha T.; Zhu Z.X.; Chen J.

Journal: Experimental Neurology

Publisher: Academic Press Inc.

Publication Date: August 2024

Volume / Issue: Volume 378

Article No.: 114820

ISSN: 144886

DOI: 10.1016/j.expneurol.2024.114820

Scopus: View on Scopus

PubMed: 38789025

Document Type: Article

Access: All Open Access; Bronze Open Access; Green Open Access

Authors and Affiliations

El-Araby R.E., Division of Oral Biology, Tufts University School of Dental Medicine, Boston, 02111, MA, United States, Theodor Bilharz Research Institute, Ministry of scientific Research, Cairo, Egypt; Wasif K., Division of Oral Biology, Tufts University School of Dental Medicine, Boston, 02111, MA, United States, Department of Human Physiology, Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, 02215, MA, United States; Johnson R., Division of Oral Biology, Tufts University School of Dental Medicine, Boston, 02111, MA, United States, Department of Human Physiology, Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, 02215, MA, United States; Tu Q., Division of Oral Biology, Tufts University School of Dental Medicine, Boston, 02111, MA, United States; Aboushousha T., Theodor Bilharz Research Institute, Ministry of scientific Research, Cairo, Egypt; Zhu Z.X., Division of Oral Biology, Tufts University School of Dental Medicine, Boston, 02111, MA, United States; Chen J., Division of Oral Biology, Tufts University School of Dental Medicine, Boston, 02111, MA, United States, Department of Genetics, Molecular and Cell Biology, Tufts University School of Medicine, Graduate School of Biomedical Sciences, 136 Harrison Ave, M&V 830, Boston, 02111, MA, United States

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms of dementia. The limited efficacy of drugs for the treatment of neurodegenerative diseases reflects their complex etiology and pathogenesis. A novel in vitro model may help to bridge the gap between existing preclinical animal models and human clinical trials, thus identifying promising therapeutic targets that can be explored in upcoming clinical trials. By assisting in the identification of the mechanism of action and potential dangers, in vitro testing can also shorten the time and expense of translation. Aim: As a result of these factors, our objective is to develop a powerful and informative cellular model of AD within a short period of time. Through triggering the MAPK and NF-κβ signaling pathways with the aid of small chemical compounds (PAF C-16 and BetA), respectively, in mouse microglial (SIM-A9) and neuroblast Neuro-2a (N2a) cell lines. Results: PAF C-16, initiated an activation effect at a concentration of 3.12 nM to 25 nM in the SIM-A9 and N2a cell lines after 72 h. BetA, activated the NF-κβ pathway with a concentration of 12.5 nM to 25 nM in the SIM-A9 and N2a cell lines after 72 h. The combination of the activator chemicals provided suitable activation for MEK1/2-ERK and NF-κβ in more than three subcultures. Activators significantly initiate APP and MAPT gene expression, as well as the expression of proteins APP, β. Amyloid, tau, and p-tau. The activation of the targeted pathways leads to significant morphological changes. Conclusion: We can infer that the MEK1/2-ERK and NF-κβ pathways, respectively, are directly activated by the PAF C-16 and BetA chemicals. The activation of MEK1/2-ERK pathway results in the activation of the APP gene, which in turn activates the β. Amyloid protein, which in turn results in plaque. Furthermore, NF-κβ activation results in the activation of the MAPT gene, which leads to Tau and p-Tau protein activation, which ultimately results in tangles. This can be put into practice in just three days, with a high level of activity and stability that is passed down to the next three generations (subculture), with significant morphological changes. In microglial and neuroblast cell lines, we were successful in creating a novel AD-cell model. © 2024 Elsevier Inc.

Keywords

Alzheimer's disease; Cell model; MEK1/2-ERK; NF-κβ; Small chemical molecules; Alzheimer Disease; Animals; Cell Line; Dose-Response Relationship, Drug; Humans; Mice; Microglia; NF-kappa B; tau Proteins; amyloid beta protein; betulic acid; immunoglobulin enhancer binding protein; mitogen activated protein kinase kinase 1; mitogen activated protein kinase kinase 2; phosphoprotein; tau protein; thrombocyte activating factor; animal cell; apoptosis; APP gene; Article; cell activation; cell culture; cell protection; cell structure; cell viability; concentration (parameter); controlled study; gene; gene expression; in vitro study; MAPT gene; microglial cell culture; mouse; Neuro-2a cell line; NF kB signaling; nonhuman; protein expression; protein function; protein localization; protein phosphorylation; protein stability; sim a9 cell line; time factor; translational research; animal; dose response; drug effect; genetics; human; metabolism; pathology

Citation Information

Scopus Citations: 3

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