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- Title
Scavenger receptor control of chromogranin A-induced microglial stress and neurotoxic cascades
- Authors
Hooper, Claudie; Fry, Victoria A.H.; Sevastou, Ioanna G.; Pocock, Jennifer M.
- Abstract
Abstract: 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.
- Subjects
ALZHEIMER'S disease; MICROGLIA; CHROMOGRANINS; GLYCOPROTEIN synthesis; APOPTOSIS; NEUROTOXICOLOGY; NEURODEGENERATION; PEPTIDES
- Publication
FEBS Letters, 2009, Vol 583, Issue 21, p3461
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2009.09.049