Table 1.

Studies and findings on the uptake and release of a-Syn by neurons, glia, and brain barrier cell types

Cell type	a-Syn transport	References
Blood–brain barrier (BBB)	1) Astrocytes: Endogenously expresses a-Syn. Astrocytes take up a-Syn by endocytosis; inflammatory activation occurs upon uptake of a-Syn aggregates. Astrocytes also secrete free a-Syn.	Braak et al., 2007 [3]
	2) Endothelia: endothelia of cerebral blood vessels express a-Syn endogenously. No detectable expression of a-Syn was found in BBB endothelia.	Kim et al., 2008 [23]
	3) Perictyes: Unknown	Lee et al., 2010a [35]
	4) Basal Lamina: Unknown	Lee et al., 2010b [36]
		Kim et al., 2013 [37]
		Tamo et al., 2002 [38]
Blood-CSF barrier (BCSFB)	Choroid Epithelia: Immortalized Z310 cells express a-Syn endogenously. Z310 cells uptake free a-Syn; clathrin is upregulated during a-Syn exposure. Primary CP epithelia from rat express a-Syn endogenously and take up free a-Syn.	Bates et al., 2012 [46]
		Bates et al., 2013 [49]
Neurons	Neurons are capable of both the uptake and secretion of a-Syn. Free and aggregated a-Syn can be secreted and taken up by neurons. Cell-to-cell transmission can occur between neurons or with multiple glial types (e.g. astrocytes, microglia, etc.)	Lee et al., 2005 [15]
		Lee et al., 2013 [17
		Desplats et al., 2009 [28]
		Lee et al., 2008a [30]
		Freeman et al., 2013 [31
		Büchel et al., 2013 [32]
Glia (excl. astrocytes)	1) Microglia: Microglia take up free and toxic a-Syn aggregates from interstitial fluid. Inflammatory activation upon uptake of a-Syn.	Wakabayashi et al., 2000 [33]
	2) Oligodendrocytes: Uptake of aggregated a-Syn was shown to be clathrin-dependent. Consequently, intracellular inclusions containing a-Syn can occur	Kisos et al., 2012 [55]
		Lee et al., 2008b [56]