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.

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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.