miR-98-5p Acts as a Target for Alzheimer's Disease by Regulating Aβ Production Through Modulating SNX6 Expression
Qiushi Li1, Xidong Li1, Li Wang2
1Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People's Republic of China.
Abstract:
Accumulation of amyloid β-peptide (Aβ) in the brain of Alzheimer disease (AD) patients is believed to be the main pathological feature of the disease. Meanwhile, miR-98-5p dysregulation was found in AD. However, whether miR-98-5p is involved in the accumulation of Aβ in AD, the underlying molecule mechanism remains unclear. In the present study, we confirmed that miR-98-5p negatively regulated sorting nexin 6 (SNX6) expression by targeting the 3'-UTR of SNX6 mRNA. Downregulation of miR-98-5p alleviated Aβ-induced viability inhibition and decreased apoptosis in SK-N-SH and SH-SY5Y cells by upregulating SNX6 expression. Furthermore, downregulation of miR-98-5p decreased SNX6-dependent levels of Aβ40, Aβ42, β-site APP-cleaving enzyme 1 (BACE1), soluble amyloid precursor protein β (sAPPβ), and membrane-associated APP β-carboxyl terminal fragment (βCTF) in SK-N-SH and HEK293 cells. Our findings demonstrate that miR-98-5p modulates SNX6 expression and thus plays a critical role in accumulation of Aβ. Therefore, miR-98-5p may be a novel therapeutic target for AD.
Insights
MicroRNA-98-5p dysregulation is linked to Alzheimer's disease (AD). This study reveals miR-98-5p targets SNX6, impacting amyloid-beta (Aβ) accumulation and offering a potential therapeutic target for AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) peptide accumulation in the brain.
- Dysregulation of microRNA-98-5p (miR-98-5p) has been observed in AD patients.
- The precise role of miR-98-5p in Aβ accumulation and its molecular mechanisms in AD remain largely unknown.
Purpose of the Study:
- To investigate the role of miR-98-5p in the regulation of amyloid-beta (Aβ) accumulation in Alzheimer's disease (AD).
- To elucidate the molecular mechanism by which miR-98-5p influences Aβ pathology.
- To evaluate miR-98-5p as a potential therapeutic target for AD.
Main Methods:
- Confirmation of miR-98-5p targeting of sorting nexin 6 (SNX6) mRNA via 3'-UTR analysis.
- Assessment of cell viability and apoptosis in neuronal cell lines (SK-N-SH, SH-SY5Y) under varying miR-98-5p and SNX6 expression levels.
- Quantification of Aβ40, Aβ42, BACE1, sAPPβ, and βCTF levels in response to miR-98-5p modulation in HEK293 and SK-N-SH cells.
Main Results:
- miR-98-5p was confirmed to negatively regulate SNX6 expression by binding to the 3'-UTR of SNX6 mRNA.
- Downregulation of miR-98-5p increased cell viability and reduced apoptosis in AD models by upregulating SNX6.
- Reduced miR-98-5p levels led to decreased levels of Aβ40, Aβ42, BACE1, sAPPβ, and βCTF, mediated by SNX6.
Conclusions:
- miR-98-5p directly modulates SNX6 expression, playing a significant role in the regulation of amyloid-beta (Aβ) accumulation.
- The miR-98-5p/SNX6 pathway represents a critical mechanism influencing Aβ pathology in Alzheimer's disease.
- miR-98-5p emerges as a promising novel therapeutic target for Alzheimer's disease treatment.
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