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Chagas' disease parasite promotes neuron survival and differentiation through TrkA nerve growth factor receptor
Author(s) -
Chuenkova Marina V.,
PereiraPerrin Mercio
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02724.x
Subject(s) - tropomyosin receptor kinase a , nerve growth factor , low affinity nerve growth factor receptor , neurotrophin , biology , neurite , autophosphorylation , microbiology and biotechnology , receptor tyrosine kinase , tropomyosin receptor kinase c , neuroscience , cancer research , kinase , receptor , protein kinase a , platelet derived growth factor receptor , growth factor , genetics , in vitro
Abstract TrkA is a receptor tyrosine kinase activated primarily by nerve growth factor (NGF) to regulate differentiation, survival, and other important functions of neurons. Given the critical role TrkA plays in neural maintenance, it may be that microbial invaders of the nervous system utilize this receptor to reduce tissue damage for maximizing host‐parasite equilibrium. Candidate pathogens could be those, like Trypanosoma cruzi, which may produce relatively little brain or nerve damage in long‐lasting infections. We show here that T. cruzi , via its neuraminidase, binds TrkA in a NGF‐inhibitable manner, induces TrkA autophosphorylation, and, through TrkA‐dependent mechanisms, triggers phosphatidylinositol 3‐kinase (PI3K)/Akt kinase signaling, cell survival, and neurite outgrowth. Unlike NGF, the neuraminidase does not react with the apoptosis‐causing pan‐neurotrophin receptor p75 NTR . Therefore, these studies identify a novel and unique TrkA ligand in a microbial invader of the nervous system, raising the thus far unsuspected prospect of TrkA underlying clinical progression of an important human infectious disease .