Table 1.
Activation profile of αSyn-stimulated glial cells
| αSyn | Co-stimulation | Cytokines, receptors or proteins affected | Pathways involved | Stimulated cells | Effect | Ref. |
|---|---|---|---|---|---|---|
| Wt, A30P, E46K, A53T | IFN-gamma; | ↑ ICAM-1, ↑T IL-6 | P38, JNK, ERK1/2, MAPK | Human astrocytes and U-373 MG astrocytoma cells | [93] | |
| Wt, A30P, E46K, A53T, Δ71–82 | IFN-gamma; | ↑ TNF-α (but only A53T w/o IFN∼y), ↑ IL-1β | Human microglia | Reduced monocytic cell viability, but only with IFN-gamma; | [57] | |
| Wt | IFN-gamma; | P38, JNK, ERK1/2, MAPK | Human microglia | ↓ Viability dopaminergic cells | [57] | |
| Aggregated Wt | ↑ Extracellular O2, ↑ Intracellular ROS, ↑ PEG2 | NADPH oxidase | Rat primary mes-enchepalic neuron-glia cell culture | ↓Dopamine uptake, cell loss, morphological alterations of dopaminergic cells | [54] | |
| wt | NADPH oxidase Binding Mac-1 | Rat primary mixed neu-ron-glial cell culture | ↑ O2− | [58] | ||
| A30P | ↑ Intracellular ROS | |||||
| A53T | ||||||
| Aggregated, nitrated | Microglia (C57BL/6J mice) | ↑ H2O2 | [60] | |||
| Aggregated versus non-aggregated, nitrated Wt | ↓Actin, galectin 3 and 14-3-3 sigma | NF-kB | Microglia (C57BL/6J mice) | [56] | ||
| ↑ Biliverdin reduc-tase calmodulin and ferritin light chain | ||||||
| ↑ Glutamate and extracellular Cys | ||||||
| ↓ Intracellular glutamate and intracellular Cys and GSH (No changes with unaggregated N-αSyn) | ||||||
| Aggregated, Nitrated Wt | ↑ TNF-a | NF-kB (↑ mRNA of Tnf, Ccl2,116, II-β, Nfkb) | Microglia (C57BL/6J mice) | ↑ Dopaminergic cell death (less for non-nitrated, only with aggregated αSyn) | [61] | |
| ↑ IL-6, ↑ MCP-1, ↑ IFN-gamma; | MAPK (↑ mRNA of Fos, Raf1) | |||||
| ↑ Hsp70, SOD, Peroxiredoxins 1, 4, and 5 | ||||||
| ↓ Aconitase and ↑ calmodulin | ||||||
| β-actin, L-plas-tin, α-tubulin | ||||||