miR-29a/b1 Regulates BACE1 in Aluminum-Induced Aβ Deposition in Vitro.

Abstract

Aluminum is an environmental neurotoxin that comes extensively in contact with human beings. Animal and human studies demonstrated that aluminum exposure increases the deposition of beta amyloid proteins in the brain as it was observed in Alzheimer's disease. The purpose of this study was to investigate whether miR-29a/b1 affected the expression of beta-secrete enzymes (BACE1) in the process of amyloid β-protein (Aβ) deposition caused by aluminum exposure. The study was performed using two different cell lines. Our results showed that after rat primary cortical neurons were exposed to aluminum, BACE1 gene and protein levels increased to different degrees, and the expression level of Aβ1-42 increased. In aluminum-exposed groups, the expression of miR-29a and miR-29b1 decreased, while the expression of amyloid protein Aβ1-42 and BACE1 increased. In miRs transfection groups, the expression of amyloid protein Aβ1-42 and BACE1 decreased. Aluminum may affect the expression of BACE1 by lowering miR-29a and miR-29b1. AEK293 cells were utilized in this research since they present elevated levels of miR-29a and miR-29b1. After HEK293 cells were exposed to aluminum alone, BACE1 mRNA and BACE1 protein expression levels increased with the increase of aluminum exposure dose (p < 0.05), and the level of Aβ1-42 also increased (p < 0.05). Compared with the group exposed to aluminum alone at the same doses, the expression levels of BACE1 mRNA and BACE1 protein in the miRs transfected plus aluminum-exposed groups significantly decreased (p < 0.05), and the level of Aβ1-42 also decreased (p < 0.05). This result is consistent with the investigation in rat primary neurons. The results of two types of cells showed that aluminum may cause abnormal down-regulation of the expressions of miR-29a and miR-29b1, thus negatively regulating the increase of BACE1 expression and finally leading to the increase of Aβ.

• Authors: Huan Li, Qun Liu, Xingli Xue, Xiaoting Lu, Jing Song, Chanting He, Yanxia Hao, Jisheng Nie, Qinli Zhang, Yue Zhao, Baolong Pan, Linping Wang, Qiao Niu
• Journal: ACS chemical neuroscience (ACS Chem Neurosci) Vol. 12 Issue 17 Pg. 3250-3265 (09 01 2021) ISSN: 1948-7193 [Electronic] United States
• PMID: 34415727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• MicroRNAs
• Aluminum
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases
• BACE1 protein, human

Topics

• Aluminum (toxicity)
• Alzheimer Disease
• Amyloid Precursor Protein Secretases (genetics)
• Amyloid beta-Peptides
• Animals
• Aspartic Acid Endopeptidases (genetics)
• HEK293 Cells
• Humans
• MicroRNAs (genetics)
• Rats