Multiple lines of evidence indicate that cerebral amyloid protein plays a key role in pathogenesis of neurodegenerative disease, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and etc1. Studies have shown that misfolding and local concentration of amyloid lead to formation of amyloid aggregates directly related to neurodegenerative diseases. Abnormal assembly of amyloid leads to the formation of senile plaques and is an important pathological hallmarks of severe neurodegenerative diseases2. Recently, research indicates that self-assembly of amyloid monomers forms oligomeric species and amyloid fibrils in vitro, and they are toxic to cells. However, the cause of the presence of amyloid as a toxic molecular species of seeds remains unknown. In vitro, different strains can be produced by varying salt concentration, temperature and pH, and these strains can form different phenotypes when injected into mouse brains3. In vivo, a large number of phosphorylated proteins are present in the senile plaques of patient samples. Therefore, studies have suggested that phosphorylated modified amyloid may cause it to form different strains and is the key to disease progression4. In order to study the important role of phosphorylation on the structure and function of amyloid protein, Alzheimer’s disease related protein β-amyloid with phosphorylated at Ser8 (pS8Aβ) and Parkinson’s disease related protein α-Synuclein with phosphorylated at Ser129 (pS129α–Syn) were synthesized. The results indicate that phosphorylation results in the formation of different strains of amyloid, respectively. We have also demonstrated that strains formed from phosphorylated monomers are more cytotoxic than non-phosphorylated monomers.

Phosphorylated amyloid protein forms different stains leading to neurodegenerative diseases

2019 Fall National Meeting

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