Supramolecular Non-Amyloid Intermediates in the Early Stages of α-Synuclein Aggregation

  • Jonathan A. Fauerbach, Dmytro A. Yushchenko, Sarah H. Shahmoradian, Wah Chiu, Thomas M. Jovin, Elizabeth A. Jares-Erijman
  • Biophysical Journal, March 2012, Elsevier
  • DOI: 10.1016/j.bpj.2012.01.051

Key forms of alpha synuclein revealed by AFM and cryo-ET

What is it about?

Parkinson's disease involves the aggregation of alpha synuclein (AS) protein. Using atomic force microscopy (AFM) and cryo-electron tomography (cryo-ET) as visualization tools, we identify and describe distinct AS structures that mediate the early stages of aggregation and provide mechanistic insight for this process. In total, we propose a sequential mechanism comprising molecular, colloidal, and fibrillar stages linked by reactions with temperature dependencies and distinct structures.

Why is it important?

Based on these new insights into the aggregation mechanism of alpha synuclein and its intermediates (some of which may cause and/or reinforce neurotoxicity), we anticipate novel diagnostic and therapeutic approaches to Parkinson's and related neurodegenerative diseases. Furthermore, although our data reflect in vitro work (not in tissue), we reveal 3-D tomographic images of a key alpha-synuclein intermediates in a frozen-hydrated state with no chemical fixation.

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The following have contributed to this page: Sarah Shahmoradian