%0 Journal Article
%T Exploring the Roles of Post-Translational Modifications in the Pathogenesis of Parkinson¡¯s Disease Using Synthetic and Semisynthetic Modified ¦Á-Synuclein
%J -
%D 2019
%R https://doi.org/10.1021/acschemneuro.8b00447
%X Alpha-synuclein (¦Á-syn), a small soluble protein containing 140 amino acids, is associated with the recycling pool of synaptic vesicles in presynaptic terminals. The misfolding and aggregation of ¦Á-syn is closely related to a group of neurodegenerative diseases, including Parkinson¡¯s disease (PD), which is one of the most common progressive neurodegenerative diseases. Varieties of the post-translational modifications (PTMs) of ¦Á-syn, including phosphorylation, ubiquitination, and glycosylation, have been detected in soluble and aggregated ¦Á-syn in vivo. These PTMs can have either positive or negative effects on ¦Á-syn aggregation and toxicity, which may play critical roles in PD pathogenesis. Herein, we review the advances in synthetic and semisynthetic chemistry to generate homogeneous ¦Á-syn variants with site-specific modifications. Using these modified ¦Á-syn, we gain insight into the consequences of PTMs on ¦Á-syn aggregation and other biophysical properties, which can help elucidate the role of PTMs in the pathogenesis of PD and develop potential therapies to PD
%U https://pubs.acs.org/doi/10.1021/acschemneuro.8b00447