Neurotoxicity protein kinase

Other putative effects of estrogens include preservation of autoregulatory function, an antioxidant effect, reduction of A(i production and neurotoxicity, reduced excitotoxicity, increased expression of antiapoptotic factor bcl-2, and activation of mitogen-activated protein kinase pathways. Also, there is overwhelming data indicating that estrogens enhance survival of neurons both in vitro and in vivo (Green and Simpkins, 2000). 

Lyso-PtdCho is not simply a lipid metabolite producing neurotrophic and neurotoxic effects. It participates in many signal transduction processes. Lyso-PtdCho activates protein kinases such as protein kinase C, protein kinase A, and c-jun terminal kinase. Lyso-PtdCho stimulates phospholipase D and inhibits CTP-phosphocholine cytidylyltransferase (Gomez-Munoz et al., 1999 Boggs et al., 1995). Lyso-PtdCho acts as an agonist for certain G-protein coupled receptors and can be converted to another bioactive lipid, lyso-phosphatidic acid. 

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...

Han, Y.S., Zheng, W.H., Bastianetto, S., Chabot, J.G., and Quirion, R., Neuroprotective effects of res veratrol against beta-amyloid-induced neurotoxicity in rat hippocampal neurons Involvement of protein kinase C. Br J Pharmacol, Mar, 141(6), 997-1005, 2004. 

Wang, J.Y., Shum, A.Y., Ho, Y.J. (2003). Oxidative neurotoxicity in rat cerebral cortex neurons synergistic effects of H2O2 and NO on apoptosis involving activation of p38 mitogen-activated protein kinase and caspase-3. J. Neurosci. Res. 72 508-19. 

Hoshi M, Sato M, Matsumoto S, Noguchi A, Yasutake K, Yoshida N, Sato K (2003) Spherical aggregates of beta-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3beta. Proc Nad Acad Sci USA 100 6370-6375. 

Takashima A, Noguchi K, Sato K, Hoshino T, Imahori K (1993) Tan protein kinase 1 is essential for amyloid beta-protein-induced neurotoxicity. Proc Natl Acad Sci USA 90 7789-7793. 

Neurotoxicity induced by oxidised low-density-lipoprotein in cultures of embryonic mouse striatal neurones was neither reduced nor enhanced by inhibiting extracellular signal-regulated kinases 1/2 activation with mitogen-activated protein kinase kinase inhibitors, suggesting that this cascade is unlikely to be involved in either oxidised low-density-lipoprotein toxicity or the protective effects of flavonoids (SCHROETER etal. 2001). 

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