Poster Presentation 13th Australian Peptide Conference 2019

Phosphorylation of α-synuclein induces distinct strains and propagation properties (#169)

Chuqiao Liang 1 , Mengrong Ma 1 , Yan-Mei Li 1
  1. Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, P. R. China

Synucleinopathies, including Parkinson's disease (PD) and Lewy bodies dementia, is a series of degenerative diseases characterized by α-synuclein (α-Syn) misfolding and abnormal aggregation[1]. The inclusions of α-Syn in Lewy bodies (LBs) and dystrophic neurites (Lewy neurites) are a pathological hallmark of PD[2].In recent years, many studies have shown that the endogenous α-Syn displays prion-like properties and act as seeds transmitting from cell to cell in cell culture and living animals[3]. Such transmission properties of different strains may explain why the same protein induces different clinical phenotypes of the synucleinopathies. Previously, researchers found that changes in the solution or seeding serval cycles may impact on the strains type[4]. Yet more factors underlined should be identified. As the main form of α-Syn in the pathological process, phosphorylated α-Syn at serine 129 (pS129 α-Syn) may be associated with multiple strain formation[5]. Hence, we synthesized pS129 α-Syn and characterized that pS129 α-Syn differs in aggregation and propagation process with wild type protein. These evidence raises that post-translational modification of α-Syn induced structurally distinct protein strains and are functionally more toxic. These results indicated the importance of protein post modification in the pathological process of the disease[6].

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