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Curr Mol Med ; 15(10): 932-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26391552

RESUMO

Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) also known as Autotaxin, is a secreted lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) into Lysophosphatidic acid (LPA). LPA is the bioactive product of ENPP2 enzyme, which induces diverse signalling pathways via six LPA-G-protein coupled receptors (GPCRs). ENPP2 is an essential protein for normal development and its altered expression is associated with various human diseases. Cellular ENPP2 silencing results in lethality at the embryonic stage in mice. Initially, it is identified as an autocrine factor in melanoma cells. Different research groups are currently exploring to understand the multifaceted role of ENPP2 in various processes such as embryonic and neural development, migration, invasion, differentiation, proliferation, angiogenesis, and survival. Altered expression of ENPP2 is also associated with various diseases like inflammation, cancer, fibrosis, rheumatoid arthritis and neural defects. In this article, we have summarized structural aspects of ENPP2 and biochemical functions associated with its diverse cellular roles in various human diseases including cancer and Alzheimer's disease (AD). In addition, keeping in view and advocating findings, a note on various phytochemicals and synthetic inhibitors, which are currently explored as therapeutic agents targeting functions of ENPP2 for the treatment of various human diseases is also presented.


Assuntos
Doença de Alzheimer/genética , Artrite Reumatoide/genética , Neoplasias/genética , Neovascularização Patológica/genética , Diester Fosfórico Hidrolases/genética , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/enzimologia , Artrite Reumatoide/patologia , Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Genes Letais , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/patologia , Neovascularização Patológica/enzimologia , Neovascularização Patológica/prevenção & controle , Diester Fosfórico Hidrolases/química , Diester Fosfórico Hidrolases/deficiência , Compostos Fitoquímicos/farmacologia , Mapeamento de Interação de Proteínas , Estrutura Terciária de Proteína , Receptores de Ácidos Lisofosfatídicos/genética , Receptores de Ácidos Lisofosfatídicos/metabolismo , Transdução de Sinais
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