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Scavenger receptor control of chromogranin A‐induced microglial stress and neurotoxic cascades
Author(s) -
Hooper Claudie,
Fry Victoria A.H.,
Sevastou Ioanna G.,
Pocock Jennifer M.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.09.049
Subject(s) - neurotoxicity , microglia , scavenger receptor , chromogranin a , chemistry , neurodegeneration , nitric oxide synthase , microbiology and biotechnology , receptor , rage (emotion) , nitric oxide , inflammation , medicine , endocrinology , biology , biochemistry , neuroscience , immunology , toxicity , lipoprotein , immunohistochemistry , disease , organic chemistry , cholesterol
Chromogranin A (CgA), a neuroactive glycoprotein, is associated with microglial activation cascades implicated in neurodegeneration. Here we show that CgA‐dependent inducible nitric oxide synthase (iNOS) expression and stress responses in microglia involved signalling via scavenger receptors (SR), since SR class‐A (SR‐A) ligands blocked iNOS expression, mitochondrial depolarisation, apoptosis and glutamate release. Furthermore, block of SR‐A ameliorated CgA‐induced microglial neurotoxicity. In contrast, block of CD36, or the receptor for advanced glycation end products (RAGE) did not prevent CgA‐induced microglial activation and neurotoxicity. Thus, manipulation of specific scavenger receptor‐coupled signalling pathways may provide avenues for therapeutic intervention in neurodegenerative diseases implicating microglial activation with chromogranin peptides.