Protein Clearance Mechanisms of Alpha-Synuclein and Amyloid-Beta in Lewy Body Disorders

Figure 1

Intra- and extraneuronal mechanisms of protein clearance. The main intracellular pathways for the degradation and recycling of proteins are the ubiquitin/proteasome system (UPS) and the autophagy-lysosomal pathway (microautophagy, macroautophagy, and chaperone-mediated autophagy (CMA)). Extracellular clearance pathways include interaction of neurons with astro- and microglia, and with infiltrating macrophages, autoantibodies, and protein transport from the parenchyma to the cerebrospinal fluid and across the blood-brain barrier. The engulfment of misfolded proteins by astro- and microglia triggers the release of proinflammatory cytokines and chemokines as well as reactive oxygen/nitrogen species, which may, under pathological conditions, further promote neuronal dysfunction and degeneration.