Figure 3. Blood-brain barrier (BBB) breakdown promotes neurodegeneration.
BBB breakdown is characterized by pericyte and endothelial degeneration, with loss of tight and adherens junctions and increased bulk flow transcytosis. BBB breakdown leads to the entry of microbial pathogens, accumulation of neurotoxic material faulty BBB transport, red blood cell extravasation and the release of neurotoxic free iron (Fe2+), which generates reactive oxygen species and oxidative stress. Inflammatory and immune responses lead to the generation of autoantibodies. CMT, solute carrier-mediated transport; ECS, extracellular spaces, L-DOPA, L-3,4-dihydroxyphenylalanine; RMT, receptor-mediated transcytosis.