Introduction: Druggable Lipid Signaling Pathways
Lipids are essential for life. They store energy, constitute cellular membranes, serve as signaling molecules, and modify proteins. In the long history of lipid research, many drugs targeting lipid receptors and enzymes that are responsible for lipid meta
- PDF / 176,804 Bytes
- 4 Pages / 504.567 x 720 pts Page_size
- 37 Downloads / 172 Views
Introduction: Druggable Lipid Signaling Pathways Yasuyuki Kihara
Abstract
Lipids are essential for life. They store energy, constitute cellular membranes, serve as signaling molecules, and modify proteins. In the long history of lipid research, many drugs targeting lipid receptors and enzymes that are responsible for lipid metabolism and function have been developed and applied to a variety of diseases. For example, non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications for fever, pain, and inflammation. The NSAIDs block prostaglandin production by inhibiting cyclooxygenases. A recent innovative breakthrough in drug discovery for the lipid biology field was the development of the sphingosine 1-phosphate receptor modulators (fingolimod, siponimod and ozanimod) for the treatment of multiple sclerosis, which were approved by the United States Food and Drug Administration in 2010, 2019 and 2020, respectively. This review series of “Druggable Lipid Signaling Pathways” provides 9 outstanding reviews that summarize the currently available drugs that target lipid signaling pathways and also outlines future directions for drug discovery. The review chapters include lipid signaling pathways (prostanoids, leukotrienes, epoxy Y. Kihara (*) Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA e-mail: [email protected]
fatty acids, sphingolipids, lysophospholipids, endocannabinoids, and phosphoinositides) and lipid signaling proteins (lysophospholipid acyltransferases, phosphoinositide 3-kinase, and G protein-coupled receptors (GPCRs)). Drugs targeting lipid signaling pathways promise to be life changing magic for the future of human health and well-being. Keywords
Lipid mediator · Drug discovery · Pharmacology · Biochemistry · Molecular biology
The lipid bilayer membrane that protects DNA from external stress is essential for DNA inheritance and cell survival [1]. Membrane lipids contain glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol), glycerolipids (mono-, ditri-acyl-glycerols), sphingolipids, and sterol lipids [2–4]. Membrane glycerophospholipids are de novo synthesized from glycerol-3-phosphate (known as the Kennedy pathway), which produces phosphatidic acid (PA) via lysophosphatidic acid (LPA) by the sequential actions of glycerol-3-phosphate acyltransferase and LPA acyltransferase (LPAAT). Phospholipases liberate fatty acyls from the glycerophospholipids,
© Springer Nature Switzerland AG 2020 Y. Kihara (ed.), Druggable Lipid Signaling Pathways, Advances in Experimental Medicine and Biology 1274, https://doi.org/10.1007/978-3-030-50621-6_1
1
2
whose diversity is generated by lysophospholipid acyltransferases (known as Land’s cycle) [5–8]. Liberated fatty acyls are further metabolized by cyclooxygenases (COXs), lipoxygenases (LOs), and cytochrome P450, resulting in the generation of prostanoids, leukotrienes, and epoxy fatty acids, respectively [9–11]. Drug discoveries for lysophospholipid acyltransfe
Data Loading...
