Leicester’s Titan Krios Cryo-electron microscope helps in groundbreaking discovery

The Titan Krios Cryo-electron microscope, based at the Leicester Institute of Structural and Chemical Biology, has provided a significant part of the data that enabled researchers to understand the structural basis of chronic traumatic encephalopathy (CTE), a head injury-associated neurodegenerative disease often called 'punch drunk syndrome'.

In the study, published in the journal Nature, researchers at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) have revealed the atomic structures of the abnormal tau filaments associated with CTE and found that they differ in structure from those seen in Alzheimer’s disease.

CTE is associated with repeated blows to the head, particularly in relation to contact sports, such as boxing, rugby and football. The symptoms of CTE include behavioural changes, confusion and memory loss. The exact causes of the disease are not fully understood however, and it is not known why only some people exposed to repeated head injury appear to develop the disease.

The research involved scientists extracting tau filaments from the brains of three individuals with CTE post-mortem - one former professional American football player and two former professional boxers. CTE can currently be diagnosed only after death, since brain tissues have to be removed and analysed to confirm presence of the disease.

The filaments were then imaged using the cryo-electron microscopy facilities at the LMB, Diamond Light Source and the University of Leicester. The team found identical tau structures from the three patients with CTE but they were different from those seen in Alzheimer’s.

Sjors Scheres, a research leader at the MRC LMB and lead author of the study, said: “We don’t know the chemical nature of these molecules yet, but we suspect they may play a role in the assembly of tau into filaments, and that their abundance may determine why some individuals develop CTE and others do not. The next stage of our research will be to identify these molecules and understand more about their role in tau assembly, as they may represent a possible target for drug development.”

Dr Christos Savva, the facility manager of the Midlands Regional Cryo-EM Facility, said: “Leicester is delighted to have been able to work with researchers from the MRC LMB in Cambridge to contribute to this groundbreaking discovery.

“This is just one of several high-resolution structures that have been determined with data from the new microscope and we are very proud of what has been achieved by the facility since its opening last April. Using this microscope and the power of Cryo-EM, we are solving many structures of proteins involved in disease and this study is a great example of what can be achieved.”

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