Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Neshan, Masouda | Malakouti, Seyed Kazemb | Kamalzadeh, Leilab | Makvand, Minaa | Campbell, Arezooc | Ahangari, Ghasema; *
Affiliations: [a] Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran | [b] Mental Health Research Center, Tehran Institute of Psychiatry – School of Behavioral Sciences and Mental Health, Iran University of Medical Sciences, Tehran, Iran | [c] Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, USA
Correspondence: [*] Correspondence to: Professor Ghasem Ahangari, Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, P.O. Box: 1497716316, Tehran, Iran. Tel.: +98 2144787384; Fax: +98 2144787399; E-mail: [email protected].
Abstract: Background:Late-onset Alzheimer’s disease (LOAD) is associated with many environmental and genetic factors. The effect of systemic inflammation on the pathogenesis of neurodegenerative diseases such as AD has been strongly suggested. T helper cells (Th) are one of the important components of the immune system and can easily infiltrate the brain in pathological conditions. The development of each Th-subset depends on the production of unique cytokines and their main regulator. Objective:This study aimed to compare the mRNA levels of Th-related genes derived from peripheral blood mononuclear cells of LOAD patients with control. Also, the identification of the most important Th1/Th2 genes and downstream pathways that may be involved in the pathogenesis of AD was followed by computational approaches. Methods:This study involved 30 patients with LOAD and 30 non-demented controls. The relative expression of T-cell cytokines (IFN-γ, TNF-α, IL-4, and IL-5) and transcription factors (T-bet and GATA-3) were assessed using Real-time PCR. Additionally, protein-protein interaction (PPI) was investigated by gene network construction. Results:A significant decrease at T-bet, IFN-γ, TNF-α, and GATA-3 mRNA levels was detected in the LOAD group, compared to the controls. However, there was no significant difference in IL-4 or IL-5 mRNA levels. Network analysis revealed a list of the highly connected protein (hubs) related to mitogen-activated protein kinase (MAPK) signaling and Th17 cell differentiation pathways. Conclusion:The findings point to a molecular dysregulation in Th-related genes, which can promising in the early diagnosis or targeted interventions of AD. Furthermore, the PPI analysis showed that upstream off-target stimulation may involve MAPK cascade activation and Th17 axis induction.
Keywords: Alzheimer’s disease, cytokine, gene expression, LOAD, mitogen-activated protein kinase, protein-protein interaction, T helper cell, Th17 cell, transcription factor
DOI: 10.3233/JAD-210480
Journal: Journal of Alzheimer's Disease, vol. 85, no. 2, pp. 645-665, 2022
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
[email protected]
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office [email protected]
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
如果您在出版方面需要帮助或有任何建, 件至: [email protected]