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MicroRNA-4422-5p as a negative regulator of Amyloidogenic Secretases: A Potential biomarker for Alzheimer's disease
15th World Congress on DEMENTIA AND ALZHEIMER'S DISEASE
November 21, 2022 | Webinar
Mehdi Mehdizadeh
University of Medicine Sciences, Iran
Posters & Accepted Abstracts : J Clin Psychiatry Cog Psychol
Abstract:
Beta-secretase (BACE1) and Gamma-Secretase Activating Protein (GSAP) are pivotal enzymes in the cleavage of Amyloid Precursor Protein (APP). Beta-amyloid (Aß) formation is considered one of the main reasons for Alzheimer’s disease (AD) pathology. In our preliminary study, a series of microRNAs (miRs) with possible interaction with BACE1 and/or GSAP was selected using computational analysis. Our results showed that miR-4422-5p had a reduced level in the serum of AD patients. In this study, the effect of miR-4422-5p using miR-4422-5p mimic and inhibitor on BACE1 and GSAP were investigated, and a probable novel early diagnostic marker for AD was introduced. The effect of miR-4422-5p interaction with BACE1 and GSAP was evaluated via in vitro experiments using dual-luciferase assays, western blotting, and Immunocytochemistry. Luciferase assay demonstrated that miR-4422-5p mimic suppresses BACE1 and GSAP expression by directly targeting the 3′UTR of BACE1 and GSAP mRNA in HEK293T cells. Also, western blotting and immunocytochemistry confirmed the regulatory role of miR-4422-5p mimic on BACE1 and GSAP genes. miR-4422-5p mimic significantly decreased BACE1 and GSAP protein expression in SH-SY5Y and A549 cells, respectively. Moreover, miR-4422-5p-inhibitor reversed the expression processes in both cell lines. Our data suggest that miR-4422-5p may be an important regulator of both BACE1 and GSAP genes and can represent a novel potential biomarker or therapeutic target in AD. References 1. Hajjari, Seyedeh Nazanin et al. “Secretases-related miRNAs in Alzheimer's disease: new approach for biomarker discovery.” Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology vol. 38,11 (2017): 1921-1926. 2. Hajjri, Seyedeh Nazanin et al. “Beta-Amyloid-Dependent miRNAs as Circulating Biomarkers in Alzheimer's Disease: a Preliminary Report.” Journal of molecular neuroscience: MN vol. 70,6 (2020): 871-877. 3. Eslamizade, Mohammad Javad et al. “Impaired Memory and Evidence of Histopathology in CA1 Pyramidal Neurons through Injection of Aβ1-42 Peptides into the Frontal Cortices of Rat.” Basic and clinical neuroscience vol. 7,1 (2016): 31-41.
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