Lysophosphatidic acid

Originally, autotaxin was identified as a factor that stimulates cell proliferation. Later it was shown that it is indeed lysophosphatidic acid (LPA) catalysed by autotaxin, which releases lysophosphatidylcholine (LPC) from its substrate and signals via lysophospholipid receptors (LPAR) (Stand S 2018). Under physiological conditions, LPA negatively regulates autotaxin transcription. Lysophosphatidic acid induces growth factor-like responses, including stimulation of cell proliferation and chemotaxis.

LPARs are expressed in all known cell types of the CNS, where they mediate basic cellular processes such as proliferation, differentiation, migration, chronic inflammation and cytoskeletal organization. Consequently, dysregulation of the LPA content can lead to a number of CNS and PNS disorders. These include chronic inflammatory or neuropathic pain, glioblastoma multiforme (GBM), hemorrhagic hydrocephalus, schizophrenia, multiple sclerosis, Alzheimer's disease, brain damage induced by the metabolic syndrome, and cerebral oedema induced by hepatic encephalopathy. It also plays a role in macular edema, in severe depressive disorders, in stress-induced psychiatric disorders, in alcohol- and HIV-induced brain damage, in pruritus and peripheral nerve injury. ATX inhibitors are in clinical phase III (Mr DR et al.2018; Fujino H et al. 2019).

Fujino H et al (2019) Pruritus in patients with chronic liver disease and serum autotaxin levels in patients with primary biliary cholangitis. BMC Gastroenterol 24:169.

Hegade VS et al (2019) Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus. Liver Int 39:967-975.

Mr DR et al (2018) Potential Therapeutic Applications for Inhibitors of Autotaxin, a Bioactive Lipid-Producing Lysophospholipase D, in Disorders Affecting the Nervous System. ACS Chem Neurosci 9:398-400.

Macias RIR et al (2018) Role of the placenta in serum autotaxin elevation during maternal cholestasis. On J Physiol Gastrointest Liver Physiol 315:G399-G407.

Robering JW et al (2019) Lysophosphatidic acid activates satellite glia cells and Schwann cells. Glia 67:999-1012.

Stand S (2018) Pruritus, Prurigo. In: Braun-Falco`s Dermatology, Venerology Allergology G. Plewig et al (Hrsg) Springer Verlag S 587