Neurodegenerative Disease

Neurodegeneration is the progressive loss of the structure or function of neurons, including the death of neurons. Neurodegenerative diseases seriously affect human health and quality of life. Many severe diseases, including Amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease, are the result of neurodegenerative processes, which involve the progressive degeneration and/or death of neurons. So far, there is no cure for neurodegenerative diseases.

Since its breakthrough, cryogenic electron microscopy (cryo-EM) has been able to create high-resolution images of a variety of structures, including virus particles and enzymes. In contrast to X-ray crystal diffraction imaging, cryo-EM does not require the crystallization process but can still solve the high-resolution protein structures. It has been used widely in the studies of pathologic proteins that play an important role in neurodegenerative diseases. For example, in 2020, the structure of full-length prion protein fibers has been solved with high-resolution cryo-EM technology, which reveals the molecular mechanism of the transformation from cellular prion protein to pathological prion protein structure. It lays a foundation for the development of novel therapeutical drugs based on the structures of prion protein fibers.

Figure 1. Cryo-EM structure of PrP fibrils (Wang L Q, et al. 2020)

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Reference

1. Wang L Q, et al. Cryo-EM structure of an amyloid fibril formed by full-length human prion protein. Nature Structural & Molecular Biology. 2020. 27(6): 598-602.