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Parkinson’s (PD) and Alzheimer’s disease (AD) are the two most common neurodegenerative diseases in humans. They are associated with the aggregation of a-synuclein and Ab in the brain, respectively, which leads to neurodegeneration. Previous studies had demonstrated that SUMOylation of a-synuclein inhibits its aggregation and toxicity in vitro. In our attempts to produce site-specifically sumoylated a-synuclein, we discovered that truncated SUMO1 peptides are able to suppress a-synuclein aggregation even in the absence of a direct covalent interaction. Computational modeling and mutagenesis studies implicated the interaction of these SUMO1-derived peptides with the SIM-motifs of a-synuclein. Evaluation of the therapeutic efficacy of our peptides showed that they could abrogate the disease symptoms in transgenic Drosophilia and mouse PD models making them potential therapeutics of PD. Given that SIM motifs are present in Ab, we have also explored the ability of our SUMO1-derived peptides to serve as therapeutics against AD. In vivo studies showed that these peptides could inhibit Ab aggregation, while in vivo studies show edthat they are capable of reducing the appearance of neurodegeneration in transgenic C. elegans and mouse AD models. Thus, our SUMO1-derived peptides serve as a novel class of therapeutics which are capable of treating both PD and AD patients.