Propane-2-sulfonic acid octadec-9-enyl-amide, a novel PPARα/γ dual agonist, attenuates molecular pathological alterations in learning memory in AD mice

ABSTRACT

Objective

Previous studies have revealed that Propane-2-sulfonic acid octadec-9-enyl-amide(N15) exerts a protective role in the inflammatory response after ischemic stroke and in neuronal damage. However, little is known about N15 in Alzheimer’s disease (AD). The aim of this study was to investigate the effects of N15 on AD and explore the underlying molecular mechanism.

Methods

AD mice model was established by lateral ventricular injection with Aβ_25–35. N15 was daily intraperitoneal administered for 28 days. Morris Water Maze was used to evaluate the neurocognitive function of the mice. The expression of PPARα/γ, brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT3), ADAM10, PS1 and BACE1 were measured by qPCR. Aβ amyloid in the hippocampus was measured by Congo red assay. Toluidine blue staining was used to detect the neuronal apoptosis. Protein levels of ADAM10, PS1 and BACE1 were determined using immunoblotting.

Results

N15 treatment significantly reduced neurocognitive dysfunction, which also significantly activated the expression of PPARα/γ at an optimal dose of 200 mg/kg. Administration of N15 alleviated the formation of Aβ amyloid in the hippocampus of AD mice, enhanced the BDNF mRNA expression, decreased the mRNA and protein levels of PS1 and BACE1, upregulated ADAM10 mRNA and protein levels.

Conclusion

N15 exerts its neuroprotective effects through the activation of PPARα/γ and may be a potential drug for the treatment of AD.

KEYWORDS:

• Alzheimer’s disease
• β-amyloid peptide
• neuronal apoptosis
• Propane-2-sulfonic acid octadec-9-enyl-amide
• PPARα/γ

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Jingwen Li and Rengong Zhuo contributed to the conception, and designed experiments. Jiang Xun, Ying Li, Yanan Zhang, Qing Wang, Chuang Wu, Guicheng Du, Ying Zeng and Zhengmao Song carried out and analyzed experimental results. Jingwen Li, Xing Jiang and Rengong Zhuo wrote the manuscript. All authors read and approved the final manuscript.

Additional information

Funding

This study was supported by the National Science Foundation of China [No. 82002162], the Natural Science Foundation of Xiamen China [No. 3502Z202373013], the Fujian Province Science and Technology Plant Project [Nos. 2021J01344, 2023D023, 2023D025, 2023D028, 2023D029, 2023D030, 2022J05325], Xiamen Medical and Health Guidance Project [3502Z20209225, 3502Z20209228, 3502Z20214ZD1257, 3502Z20224ZD1282, 3502Z20224ZD1293, 3502Z20214ZD1326, 3502Z20209117, 3502Z20224ZD1304 and 3502Z20224ZD1301] the Fujian Province Health and Middle aged Youth Research Major Project [No. 2023ZQNZD019] and the Natural Science Foundation of Xiamen Medical College [No. K2021-01].