Matrix metalloproteinases neurotoxicity

Fig. 8.1 A schematic diagram illustrating the involvement of NF-k I in gpl20, ROS, NO, PG, IL-1/3 and TNF-a-mediated neurotoxicity. NMDA-R, N-Methyl-D-aspartate receptor, cPLA2, cytosolic phospholipase A2 lyso-PtdCho, lysophosphatidylcholine AA, arachidonic acid cAMP, cyclic adenosine monophosphate PKA, protein kinase A TNF-a, tumor necrosis factor-a TNF-a-R, TNF-a-receptor IL-1/8, interleukin-1 /3 IL-l/i-R, IL-1/8-receptor, IL-6, interleukin-6 MARK, mitogen-activated protein kinase NO, nitric oxide PG, prostaglandins EP-R, prostaglandin receptors NF-kB, nuclear factor-icB NF-kB-RE, nuclear factor-/cB-response element I/cB, inhibitory subunit of NF-icB HIV-1, human immunodeficiency virus type 1 gpl20, HIV-1 coat glycoprotein COX-2, cyclooxygenase-2 iNOS, inducible nitric oxide synthase SPLA2, secretory phospholipase A2 SOD, superoxide dismutase MMP, matrix metalloproteinase and VCAM-1, vascular adhesion molecule-1...

DOM treatment also rapidly decreases cellular GSH, which precedes neurotoxicity. This decrease is primarily due to DOM-mediated GSH efflux. DOM also induces an increase in oxidative stress as indicated by increases in ROS and lipid peroxidation products, which follow GSH efflux. Astrocytes from both genotypes are resistant to DOM-mediated neurotoxicity and present a diminished Ca2+ response to DOM-mediated toxicity (Walser et al., 2006). Exposure of neonatal rat microglia to DOM triggers the release of TNF-a and matrix metalloproteinase-9 (MMP-9) (Mayer et al., 2001). These molecules are involved in the modulation of neuroinflammation in brain (Farooqui et al., 2007). Collective evidence suggests that DOM-mediated neurodegeneration involves changes in cellular redox, oxidative stress, and increased expression of cytokines, nitric oxide synthase, NADPH diaphorase, and matrix metalloproteinase-9 (Walser et al., 2006 Chandrasekaran et al., 2004 Ananth et al., 2003a,b Mayer et al., 2001). 

Jourquin, J., Tremblay E., Decanis, N., et al., 2003. Neuronal activity-dependent increase of net matrix metalloproteinase activity is associated with MMP-9 neurotoxicity after kainate. Eur. J. Neurosci. 18,1507-1517. 

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