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Reports of Biochemistry and Molecular Biology
rbmb.net
Basic Sciences
http://rbmb.net
1
admin
2322-3480
2322-3480
10.61882/rbmb
en
jalali
1399
10
1
gregorian
2021
1
1
9
4
online
1
fulltext
en
Effects of Amyloid Precursor Protein Overexpression on NF-κB, Rho-GTPase and Pro-Apoptosis Bcl-2 Pathways in Neuronal Cells
زیست شناسی سلولی
Cell Biology
مقالات اصلی
Original Article
<div style="text-align: justify;"><strong><em>Background:</em></strong> Alzheimer’s disease (AD) is a neurodegenerative disorder that causes cognitive dysfunction. Previous studies have suggested that amyloid plaques, mainly comprising of amyloid-beta peptides, play a pivotal role in AD pathophysiology. This study focuses on the evaluation of the effects of amyloid precursor protein (APP) overexpression on NF-κB, Rho-GTPase and Bcl-2 mediated pro-apoptotic pathways in neuronal cells.<br>
<br>
<strong><em>Methods:</em></strong> A lentiviral transduction system was used to generate SH-SY5Y cells overexpressing APP. Immunoblotting was conducted to determine expression levels of NF-κB, Rho-GTPase, and Bcl-2 family proteins in the APP overexpressed cells.<br>
<br>
<strong><em>Results:</em></strong> In the NF-κB signaling pathway, APP-overexpressing SH-SY5Y cells showed that there was a reduction of p-NF-κB (p< 0.05) and IKKα. Subsequently, there was upregulation of protein expression of NF-Κb, IKKβ and IκBα. On the other hand, protein expression of RhoC (p< 0.05) and Rac1/2/3 was upregulated as compared to the control group. Meanwhile, a decrease in RhoA, Cdc42 (p< 0.05) and p-Rac1/cdc42 protein levels was observed in the APP-overexpressed group. Lastly, in the pro-apoptotic pathway, the expression of Bcl-2, Bid, Bok and Puma (p< 0.05) was up regulated in the APP-overexpressed group. Downregulation of Bad and Bim expression was observed in the APP-overexpressed as compared to the control group, and Bax expression remained unchanged in the APP-overexpressed group.<br>
<br>
<strong><em>Conclusions:</em></strong> APP overexpression regulated signaling in the NF-κB, Rho-GTPase and Bcl-2 family pathways in neuronal cells, suggesting that these are involved in promoting neuronal survival and modulating synaptic plasticity in AD. However, further studies are essential to elucidate the APP-mediated mechanism of action.<br>
</div>
Alzheimer’s disease, Amyloid precursor protein, Bcl-2 family proteins, NF-κB, Rho-GTPase.
417
425
http://rbmb.net/browse.php?a_code=A-10-505-1&slc_lang=en&sid=1
Hong Hao
Chan
100319475328460017739
100319475328460017739
No
School of Postgraduate Studies and Research, International Medical University, Kuala Lumpur, Malaysia.
Yong Qi
Leong
100319475328460017740
100319475328460017740
No
Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia.
Shee Man
Voon
100319475328460017741
100319475328460017741
No
Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia.
Meng Liy
Pan
100319475328460017742
100319475328460017742
No
Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia.
Chee Onn
Leong
cheeonn_leong@imu.edu.my
100319475328460017743
100319475328460017743
No
Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
Chooi Ling
Lim
100319475328460017744
100319475328460017744
No
Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia.
Rhun Yian
Koh
rhunyian_koh@imu.edu.my
100319475328460017745
100319475328460017745
Yes
Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia.