miR-615-3p targets SESN2 to inhibit neuronal mitophagy in an in vitro Alzheimer’s disease model by regulating the AMPK/ULK1 axis
- 1Department of Xiaolong Internal Medicine, Nanchong Psychosomatic Hospital , ,
Abstract
Background: Alzheimer’s disease (AD) is characterized by amyloid-β accumulation, mitochondrial dysfunction, and neuronal injury. miR-615-3p is upregulated in AD, but its role in regulating mitophagy remains unclear.
Methods: HT22 hippocampal neurons were treated with Aβ1-42 to establish an AD-like model. Gain-of-function and loss-of-function experiments were conducted to assess the roles of miR-615-3p and its target SESN2, which were identified through bioinformatics and dual-luciferase assays. Cell viability, apoptosis, oxidative stress, mitochondrial function, inflammatory responses, and mitophagy-related proteins were evaluated. The involvement of the AMPK/ULK1 pathway was also examined.
Results: miR-615-3p overexpression significantly reduced cell viability and ATP levels while increasing apoptosis, Aβ accumulation, lactate dehydrogenase release, reactive oxygen species production, mitochondrial membrane potential loss, and inflammatory cytokine levels. Mitophagy markers, including LC3-II/LC3-I, Parkin, and PINK1, were elevated. Mechanistically, miR-615-3p downregulated SESN2 and inhibited AMPK/ULK1 phosphorylation. SESN2 overexpression reversed these effects, restoring mitochondrial function, reducing oxidative stress and inflammation, and improving cell survival.
Conclusion: miR-615-3p aggravates neuronal injury by targeting SESN2 and regulating mitophagy through the AMPK/ULK1 pathway, suggesting a potential therapeutic target for Alzheimer’s disease.
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BibTeX
@article{jing2026mir6153p,
title = {{miR-615-3p targets SESN2 to inhibit neuronal mitophagy in an in vitro Alzheimer’s disease model by regulating the AMPK/ULK1 axis}},
author = {Yang Jing and DeKun Li and Li Chen and Song Li and Xiang Yuan},
journal = {Frontiers in molecular neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnmol.2026.1873619},
url = {https://europepmc.org/article/PMC/PMC13719307},
note = {CC BY},
}
RIS
TY - JOUR
TI - miR-615-3p targets SESN2 to inhibit neuronal mitophagy in an in vitro Alzheimer’s disease model by regulating the AMPK/ULK1 axis
AU - Yang Jing
AU - DeKun Li
AU - Li Chen
AU - Song Li
AU - Xiang Yuan
PY - 2026
DA - 2026/10/16
JO - Frontiers in molecular neuroscience
DO - 10.3389/fnmol.2026.1873619
UR - https://europepmc.org/article/PMC/PMC13719307
AB - Background: Alzheimer’s disease (AD) is characterized by amyloid-β accumulation, mitochondrial dysfunction, and neuronal injury. miR-615-3p is upregulated in AD, but its role in regulating mitophagy remains unclear. Methods: HT22 hippocampal neurons were treated with Aβ1-42 to establish an AD-like model. Gain-of-function and loss-of-function experiments were conducted to assess the roles of miR-615-3p and its target SESN2, which were identified through bioinformatics and dual-luciferase assays. Cell viability, apoptosis, oxidative stress, mitochondrial function, inflammatory responses, and mitophagy-related proteins were evaluated. The involvement of the AMPK/ULK1 pathway was also examined. Results: miR-615-3p overexpression significantly reduced cell viability and ATP levels while increasing apoptosis, Aβ accumulation, lactate dehydrogenase release, reactive oxygen species production, mitochondrial membrane potential loss, and inflammatory cytokine levels. Mitophagy markers, including LC3-II/LC3-I, Parkin, and PINK1, were elevated. Mechanistically, miR-615-3p downregulated SESN2 and inhibited AMPK/ULK1 phosphorylation. SESN2 overexpression reversed these effects, restoring mitochondrial function, reducing oxidative stress and inflammation, and improving cell survival. Conclusion: miR-615-3p aggravates neuronal injury by targeting SESN2 and regulating mitophagy through the AMPK/ULK1 pathway, suggesting a potential therapeutic target for Alzheimer’s disease.
SN - 1662-5099
ER -