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An unexpected protein aggregate in diseased and ageing brains

Protein fibrils accumulate in the brain during neurodegeneration. Cryo-electron microscopy has now uncovered fibrils of a protein not previously thought to accumulate.
  1. Hideyuki Takahashi

    1. Hideyuki Takahashi is in the Departments of Neuroscience and Neurology, Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA.

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  2. Stephen M. Strittmatter

    1. Stephen M. Strittmatter is in the Departments of Neuroscience and Neurology, Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA.

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Neurodegenerative diseases often involve the formation of insoluble protein aggregates called fibrils in the brain, with specific proteins characterizing different diseases. For example, amyloid-β fibrils form in Alzheimer’s disease, whereas α-synuclein fibrils define Parkinson’s disease. The study of these fibrils tends to follow a set path: the discovery of an aggregate in brain tissue analysed at autopsy, then analysis of its biochemistry; genetic research to pinpoint mutations associated with the abnormal protein; functional studies to investigate how the protein is altered in disease; and, finally, structural biology of the disease-related protein fibril. Writing in Nature, Schweighauser et al.1 and Jiang et al.2 turn this discovery pathway on its head. In the process of using cryo-electron microscopy at near-atomic resolution to investigate the structure of known aggregates, they have detected the presence of a previously unknown protein fibril in the brain.

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Nature 605, 227-228 (2022)

doi: https://doi.org/10.1038/d41586-022-00873-2

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Competing Interests

The authors declare no competing interests.

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