Figure 4.
Proposed mechanisms of immune involvement in neurodegeneration and neuronal repair. Damage to neurons or mutations in proteins leads to misfolded or aggregated proteins (i) while macrophage and microglia activation stimulates, for example, reactive oxygen species (ROS) production known to induce mitochondrial dysfunction that could, unchecked, lead to neuronal damage, (ii) CD8 T-cell-mediated cytotoxicity, (iii) induced Fas:FasL or perform mediated damage, and (iv) excess glutamate leading to exocitotoxicity. Neuroprotection and regeneration is afforded by cells of the immune system. T cells secrete neuroprotective factors and suppress pro-inflammatory responses, while macrophages/microglia carry out phagocytosis and astrocytes stimulate growth and repair via glial cell-derived neuronal growth factors. Endocannabinoids inhibit glutamate cytotoxicity. IL, interleukin; MMPs, matrix metalloproteinases; NO, nitric oxide; Th2, T helper 2; T reg, T regulatory.