An unexpected protein aggregate in diseased and ageing brains

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High-resolution structures of TMEM106B fibrils.

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

 

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