Alpha Synuclein: Transmission

Similar to cancer’s metastasis through the body’s tissues, α-synuclein pathology follows a prion-like propagation through the nervous system. A stereotypical pattern of α-synuclein transmission was suggested for PD, starting at the brainstem and spreading rostrally to different neocortical regions (frontal, parietal, occipital, and temporal) of the brain (Braak et al., 2003). Since then, there have been many proposed mechanisms of α-synuclein transmission: endocytosis, direct penetration, micropinocytosis, pore formation, nanotube tunneling and diffusion (Ubhi et al., 2011) (Konno et al., 2012). Masuda-Suzukake et al. (2014), studied the method of transmission by injecting recombinant α-synuclein fibrils into different areas of wild type mice brains (substantia nigra, striatum, or entorhinal cortex) and analyzing the propagation patterns and distribution of phosphorylated α-synuclein pathologies. There were unique patterns of propagation at each injection site, suggesting a location dependency that was not observed in Braak’s research. The results imply that spreading follows neural circuits and includes trans-synaptic transport. It showed that α-synuclein fibrils could be internalized by neurons and moved from axons to second order neurons. The propagation of α-synuclein occurred in both anterograde and retrograde directions depending on the brain area.