miR-34a-5p and miR-125b-5p attenuate Aβ-induced neurotoxicity through targeting BACE1
Pengxiang Li1, Ying Xu2, Baiping Wang3
1Department of Neurology, The Second Affiliated Hospital of Hainan Medical University, 570311 Haikou, Hainan, China.
Background:
Accumulation of β-amyloid (Aβ) could induce neurotoxicity in Alzheimer's disease (AD). microRNA (miR)-34a-5p and miR-125b-5p have been reported to be aberrantly expressed in AD patients. However, the roles and mechanisms of these two miRNAs in AD remain poorly understood.
Methods:
Serum samples of 27 AD patients were collected. Primary mouse cortical neurons (MCN) and Neuro2a (N2a) cells were incubated with Aβ. The expression levels of miR-34a-5p, miR-125b-5p and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) were detected by quantitative real-time polymerase chain reaction and western blot. The effect of miRNAs or epigallocatechin-3-gallate (EGCG) on Aβ-induced neurotoxicity was investigated by cell viability, Caspase 3 activity, apoptosis and intracellular ROS production. The interaction between BACE1 and miR-34a-5p or miR-125b-5p was analyzed by luciferase reporter assay.
Results:
miR-34a-5p and miR-125b-5p levels were decreased and BACE1 mRNA expression was increased in AD patients and Aβ-treated MCN and N2a cells. Addition of miR-34a-5p or miR-125b-5p attenuated Aβ-induced apoptosis and oxidative stress. BACE1 acted as a target of miR-34a-5p and miR-125b-5p and its restoration weakened the effect of miR-34a-5p or miR-125b-5p on Aβ-induced neurotoxicity. Moreover, EGCG could mitigate Aβ-induced neurotoxicity, which might be associated with miR-34a-5p and miR-125b-5p.
Conclusion:
miR-34a-5p and miR-125b-5p inhibited Aβ-induced neurotoxicity by decreasing apoptosis and oxidative stress via targeting BACE1, providing novel targets for treatment of AD.
Insights
microRNA-34a-5p and microRNA-125b-5p reduce Alzheimer's disease neurotoxicity by targeting BACE1. These microRNAs offer potential therapeutic targets for Alzheimer's disease treatment.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by neurotoxicity from beta-amyloid (Aβ) accumulation.
- Aberrant expression of microRNA (miR)-34a-5p and miR-125b-5p is observed in AD patients, but their precise roles are unclear.
Purpose of the Study:
- To investigate the roles and mechanisms of miR-34a-5p and miR-125b-5p in Aβ-induced neurotoxicity.
- To explore the potential of these miRNAs as therapeutic targets for AD.
Main Methods:
- Quantitative real-time PCR and western blot were used to measure miRNA and BACE1 expression in AD patients and Aβ-treated cells.
- Cell viability, apoptosis, and oxidative stress assays assessed the effects of miRNAs and EGCG on neurotoxicity.
- Luciferase reporter assays determined the interaction between BACE1 and the studied miRNAs.
Main Results:
- miR-34a-5p and miR-125b-5p levels were decreased, while BACE1 mRNA expression was increased in AD patients and Aβ-treated cells.
- Exogenous miR-34a-5p or miR-125b-5p attenuated Aβ-induced apoptosis and oxidative stress.
- BACE1 was identified as a direct target of miR-34a-5p and miR-125b-5p, and its inhibition mediated the neuroprotective effects of these miRNAs.
Conclusions:
- miR-34a-5p and miR-125b-5p inhibit Aβ-induced neurotoxicity by targeting BACE1, reducing apoptosis and oxidative stress.
- These miRNAs represent novel therapeutic targets for Alzheimer's disease treatment.
