α-Synuclein-Assembled Synaptic Vesicle Pools at the Presynaptic Terminal: A Study of α-Synuclein Function Using a Novel Mouse Model.

Abstract

α-Synuclein is the causative gene for PARK1 and PARK4 (heterozygous triplication of SNCA) and is associated with Parkinson's disease, where it localizes to presynaptic terminals in mature neurons. Beyond Parkinson's disease, α-synuclein has also been implicated in various other neuronal disorders. In vitro studies using purified α-synuclein protein have suggested it is involved in synaptic vesicle assembly. However, its physiological function and the ultrastructure of its localization sites in presynaptic terminals remain unclear. To address this, we generated transgenic mice overexpressing human α-synuclein tagged with mKate2 (hSNCA-mKate2 mice) to investigate its in vivo role in synaptic vesicle pool formation at presynaptic terminals. These mice showed normal growth and fertility, and even at 1-yr. old, they showed no motor dysfunction compared to their wild-type littermates. Additionally, no abnormal protein aggregates indicative of neurodegeneration were observed. In this review, we summarize recent findings on the in vivo role of α-synuclein within presynaptic terminals, utilizing hSNCA-mKate2 mice in combination with in-resin correlative light and electron microscopy, electron microscopy, and immunohistochemistry.