Neurotoxic mechanisms of Aβ
| Toxic Mechanisms | Effects | Reference |
|---|---|---|
| Alteration of ion homeostasis | ||
| Potentiation of calcium channels or formation of calcium permeable channels | [Ca2+]↑ | Mattson et al., 1992; Weiss et al., 1994; Vitek et al., 1994; Lin et al., 1999;Zhu et al., 2000; Green and Peers, 2001; Lin et al., 2001 |
| Enhancement of glutamate-mediated excitotoxicity | [Ca2+]↑ | Harkany et al., 2000 |
| Inhibition of Na+/Ca2+exchanger | [Ca2+]↑ | Wu et al., 1997 |
| Selective inhibition of potassium channel | [Ca2+]↑ | Good et al., 1996 |
| Enhancement of K+ current density | [K+]↑ [Ca2+]↓ | Colom et al., 1998 |
| Impairment of Na+/K+ATPase | [Ca2+]↑ | Mark et al., 1995 |
| Generation of reactive oxygen species | ||
| Production of free radical | Lipid peroxidation, DNA oxidation, and protein oxidation | Behl et al., 1994; Butterfield et al., 1994; Mattson et al., 1995;Varadarajan et al., 2000; Koppaka and Axelsen, 2000; Monji et al., 2001 |
| Release of lipid | Michikawa et al., 2001 | |
| Activation of inflammatory response | ||
| Activation of microglia/astrocytes | Release of cytokines and chemokines | Hu et al., 1998; Tan et al., 1999; Lue et al., 2001 |
| NO generation | Akama et al., 1998; Tran et al., 2001 | |
| Activation of signaling pathway | ||
| Activation of MAPK | Tau phosphorylation | Rapoport and Ferreira, 2000 |
| Activation of JNK | Induction of Fas ligand | Morishima et al., 2001 |
| Activation of calpain 1 and Cdk5 | Tau phosphorylation | Patrick et al., 1999; Lee et al., 2000b |
| Activation of Src family tyrosine kinase | Tyrosine phosphorylation of cytoskeletal proteins (tau, microtubule-associated protein 2c) | Williamson et al., 2002 |