[HTML][HTML] The bulk of autotaxin activity is dispensable for adult mouse life

A Katsifa, E Kaffe, N Nikolaidou-Katsaridou… - PloS one, 2015 - journals.plos.org
A Katsifa, E Kaffe, N Nikolaidou-Katsaridou, AN Economides, S Newbigging, C McKerlie
PloS one, 2015journals.plos.org
Autotaxin (ATX, Enpp2) is a secreted lysophospholipase D catalysing the production of
lysophosphatidic acid, a pleiotropic growth factor-like lysophospholipid. Increased ATX
expression has been detected in a number of chronic inflammatory diseases and different
types of cancer, while genetic interventions have proven a role for ATX in disease
pathogenesis. Therefore, ATX has emerged as a potential drug target and a large number of
ATX inhibitors have been developed exhibiting promising therapeutic potential. However …
Autotaxin (ATX, Enpp2) is a secreted lysophospholipase D catalysing the production of lysophosphatidic acid, a pleiotropic growth factor-like lysophospholipid. Increased ATX expression has been detected in a number of chronic inflammatory diseases and different types of cancer, while genetic interventions have proven a role for ATX in disease pathogenesis. Therefore, ATX has emerged as a potential drug target and a large number of ATX inhibitors have been developed exhibiting promising therapeutic potential. However, the embryonic lethality of ATX null mice and the ubiquitous expression of ATX and LPA receptors in adult life question the suitability of ATX as a drug target. Here we show that inducible, ubiquitous genetic deletion of ATX in adult mice, as well as long-term potent pharmacologic inhibition, are well tolerated, alleviating potential toxicity concerns of ATX therapeutic targeting.
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