title: Heparan sulfate proteoglycan induces the production of NO and TNF-alpha by murine microglia.
abstract: BACKGROUND
  A common feature of Alzheimer's disease (AD) pathology is the abundance of activated microglia in neuritic plaques containing amyloid-beta protein (Abeta) and associated molecules including heparan sulfate proteoglycan (HSPG). Besides the role as pathological chaperone favouring amyloidogenesis, little is known about whether or not HSPG can induce microglial activation. Cultures of primary murine microglia were used to assess the effect of HSPG on production of proinflammatory molecules that are known to be present in neuritic plaques of AD.
  
  
  RESULTS
  HSPG stimulated up-regulation of tumor necrosis factor-alpha (TNF-alpha), production of inducible nitric oxide synthase (iNOS) mRNA and accumulation of TNF-alpha protein and nitrite (NO2-) in a time- and concentration-dependent manner. The effects of HSPG were primarily due to the property of the protein core as indicated by the lack of microglial accumulation of TNF-alpha and NO2- in response to denaturated HSPG or heparan sulfate GAG chains (HS).
  
  
  CONCLUSIONS
  These data demonstrate that HSPG may contribute to chronic microglial activation and neurodegeneration seen in neuritic plaques of AD.
authors: Department of Neurological Sciences, Centre for Excellence on Neurodegenerative Diseases, Dino Ferrari Center, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20122 Milan, Italy. clinneur@unimi.it
authors: Simona
authors: S
authors: Bussini
authors: Lucia
authors: L
authors: Meda
authors: Elio
authors: E
authors: Scarpini
authors: Emilio
authors: E
authors: Clementi
authors: Giancarlo
authors: G
authors: Conti
authors: Marco
authors: M
authors: Tiriticco
authors: Nereo
authors: N
authors: Bresolin
authors: Pierluigi
authors: P
authors: Baron