Scavenger receptor control of chromogranin A-induced microglial stress and neurotoxic cascades |
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Authors: | Claudie Hooper |
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Institution: | Cell Signalling Laboratory, 1 Wakefield Street, Institute of Neurology, University College London, London WC1N 1PJ, UK |
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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. |
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Keywords: | Microglia Alzheimer&rsquo s disease Neurodegeneration Cell stress Scavenger receptor |
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