Reports of Biochemistry and Molecular Biology

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;">Background: 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. Methods: 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. Results: 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. Conclusions: 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.  </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.