FEBS Letters
Volume 583, Issue 21 , Pages 3461-3466, 3 November 2009

Scavenger receptor control of chromogranin A-induced microglial stress and neurotoxic cascades

Edited by Jesus Avila

Cell Signalling Laboratory, 1 Wakefield Street, Institute of Neurology, University College London, London WC1N 1PJ, UK

Received 22 June 2009; received in revised form 17 September 2009; accepted 28 September 2009. published online 05 October 2009.

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.

Keywords: Microglia, Alzheimer’s disease, Neurodegeneration, Cell stress, Scavenger receptor

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PII: S0014-5793(09)00753-4

doi:10.1016/j.febslet.2009.09.049

FEBS Letters
Volume 583, Issue 21 , Pages 3461-3466, 3 November 2009

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