Alpha Synuclein: Localization

α-synuclein is localized specifically to the presynaptic terminal of neurons and associated with presynaptic vesicles. It is scarcely present in the cell body, dendrites, or extra synaptic sites. The protein is found in the peripheral nervous system (PNS), central nervous system (CNS), and red blood cells (Bendor et al., 2013).

α-synuclein is typically a cytosolic protein (endogenous), however, small amounts of extracellular (exogenous) protein can be found in human body fluids like cerebrospinal fluid (CSF) and blood plasma (Lee et al., 2011). Theillet et al. (2016) revealed that exogenous α-synuclein is N terminally acetylated, disordered, dynamic, and interacts with the cytoplasm to form compact structures within cells. Low amounts of monomeric and aggregated protein are naturally secreted by exocytosis (Lee et al., 2011), however, neuronal cells under cellular stress and mitochondrial dysfunction release high levels of endogenous α-synuclein to their external environment. The internal mechanism of regulating the levels of endogenous α-synuclein released from cells is based on neuronal activity and linked specifically to glutamatergic neurotransmission (Yamada and Iwatsubo, 2018). This implies that glutamate activates the post synaptic receptors and raises the levels of α-synuclein released by synaptic vessel exocytosis.