2. Academic Validation
  3. A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy

A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy

  • CNS Neurosci Ther. 2021 Apr;27(4):484-496. doi: 10.1111/cns.13573.
Jian-Tao Wang 1,  Zhong-Yu Yu 1,  Ying-Hong Tao 2,  Ying-Chao Liu 3,  Yan-Mei Wang 1,  Qi-Lin Guo 4,  Jian-Zhong Xue 5,  Xiao-Hong Wen 4,  Qian Zhang 4,  Xiao-Die Xu 4,  Cheng-Feng He 4,  Wen-Jiao Xue 4,  Jing-Chun Guo 4,  Hou-Guang Zhou 1
Affiliations

Affiliations

  • 1 Department of Geriatric Neurology of Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, China.
  • 2 Department of Medical Examination Center, Huashan Hospital, Fudan University, Shanghai, China.
  • 3 Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Jinan, China.
  • 4 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.
  • 5 Department of Neurology, Fifth Clinical Medical College of Yangzhou University, Changshu Second People's Hospital of Jiangsu Province, Changshu, China.
PMID: 33459523 DOI: 10.1111/cns.13573
Abstract

Aims: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to Autophagy.

Methods: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, Autophagy, Apoptosis, oxidative stress, cognition, and a range of inflammatory factors.

Results: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of Autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of Apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA.

Conclusion: We found that 5-PAHSA can enhance Autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice.

Keywords

5-PAHSA; autophagy; m-TOR; oxidative stress; type-2 diabetes mellitus.

Figures
Products