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Published on: July 26, 2011
LPI alleviates Alzheimer's disease pathology via the GPR55 receptor
Wenjie Xu1, Jiaqi Cao2, Yibo Liu2
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Laboratory for Clinical Medicine, Capital Medical University, Beijing, China; Department of Morphology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
None:
Lysophosphatidylinositol (LPI) is an endogenous GPR55 agonist, yet its role in Alzheimer's disease (AD) remains unclear. Here, we performed serum metabolomic profiling in 5xFAD mice and observed a reduction in multiple LPI species prior to the onset of overt Aβ pathology, and this decrease was further corroborated in human cohort samples. Exogenous LPI treatment reduced cerebral Aβ deposition, improved performance in learning and memory behavioral tasks, reduced pathological microglial aggregation, inhibited astrocyte proliferation, and ameliorated hippocampal oxidative stress. Mechanistically, administration of the GPR55 antagonist ML191 blocked the protective effects of LPI, while the GPR55 agonist O-1602 recapitulated these benefits, indicating that LPI acts through GPR55. Collectively, our findings suggest that reduced LPI represents an early metabolic vulnerability in the 5xFAD model and establish the LPI-GPR55 axis as a potential therapeutic target for early intervention in AD.
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