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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.01124

Different heat shock proteins bind α-synuclein with distinct mechanisms and synergistically prevent its amyloid aggregation

 Chunyu Jia1, 2,  Xiaojuan Ma1, 2, Zhenying Liu1, 2, Jinge Gu1, 2, Xiang Zhang1, 2,  Dan Li3* and  Shengnan Zhang1*
  • 1Shanghai Institute of Organic Chemistry (CAS), China
  • 2Chinese Academy of Sciences, China
  • 3Shanghai Jiao Tong University, China

α-Synuclein (α-Syn) forms pathological amyloid aggregates deposited in Lewy bodies and Lewy neurites in the brain of Parkinson’s disease (PD) patients. Heat shock proteins (Hsps) are the major components of the cellular chaperone network, which are responsible for preventing proteins from amyloid aggregation. Different Hsps were reported to interact with α-syn. However, the underlying mechanism of the interplay between α-syn and different Hsps remains unclear. Here, by combing NMR spectroscopy, electron microscope and other biochemical approaches, we systemically investigated the interaction between α-syn and three Hsps from different families including Hsp27, HDJ1 and Hsp104. We found that all three Hsps can weakly bind α-syn and inhibit it from amyloid aggregation. Intriguingly, different Hsps recognize distinct regions of α-syn monomer, and act synergistically in chaperoning α-syn from fibril formation in sub-stoichiometry. Our results revealed the diverse binding mechanisms employed by different Hsps to tackle α-syn, and suggested that different Hsps form a network for cooperatively chaperoning α-syn from pathological aggregation.

Keywords: Parkinson's disease (PD), α-Syn, amyloid aggregation, Heat shock protein, synergistic effect, Protein homeostasis

Received: 25 Aug 2019; Accepted: 04 Oct 2019.

Copyright: © 2019 Jia, Ma, Liu, Gu, Zhang, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Dan Li, Shanghai Jiao Tong University, Shanghai, 200240, Shanghai Municipality, China,
Dr. Shengnan Zhang, Shanghai Institute of Organic Chemistry (CAS), Shanghai, 200032, Shanghai Municipality, China,