Lysophospholipids and Their G-Coupled Protein Signaling in Alzheimer's Disease: From Physiological Performance to Pathological Impairment

Yining Hao; Min Guo; Yiwei Feng; Qiang Dong; Mei Cui

doi:10.3389/fnmol.2020.00058

Lysophospholipids and Their G-Coupled Protein Signaling in Alzheimer's Disease: From Physiological Performance to Pathological Impairment

Front Mol Neurosci. 2020 Apr 15:13:58. doi: 10.3389/fnmol.2020.00058. eCollection 2020.

Authors

Yining Hao¹, Min Guo¹, Yiwei Feng¹, Qiang Dong², Mei Cui¹

Affiliations

¹ Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.

Abstract

Lysophospholipids (LPLs) are bioactive signaling lipids that are generated from phospholipase-mediated hydrolyzation of membrane phospholipids (PLs) and sphingolipids (SLs). Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are two of the best-characterized LPLs which mediate a variety of cellular physiological responses via specific G-protein coupled receptor (GPCR) mediated signaling pathways. Considerable evidence now demonstrates the crucial role of LPA and S1P in neurodegenerative diseases, especially in Alzheimer's disease (AD). Dysfunction of LPA and S1P metabolism can lead to aberrant accumulation of amyloid-β (Aβ) peptides, the formation of neurofibrillary tangles (NFTs), neuroinflammation and ultimately neuronal death. Summarizing LPA and S1P signaling profile may aid in profound health and pathological processes. In the current review, we will introduce the metabolism as well as the physiological roles of LPA and S1P in maintaining the normal functions of the nervous system. Given these pivotal functions, we will further discuss the role of dysregulation of LPA and S1P in promoting AD pathogenesis.

Keywords: Alzheimer’s disease (AD); G-protein coupled receptor (GPCR); lysophosphatidic acid (LPA); lysophospholipids; sphingosine-1-phosphate (S1P).