Cryo-electron microscopy (cryo-EM) has emerged as a transformative technique in structural biology, driving an exponential increase in the number of structures deposited in the Protein Data Bank. Current workflows now routinely achieve the near-atomic resolution essential for understanding the molecular pathology of neurodegenerative and metabolic disorders. This provides a comprehensive overview of the field, tracing the evolution from early structural studies to modern pipelines powered by deep-learning algorithms for helical reconstruction. We address the persistent bottleneck of sample preparation, detailing the physical challenges of fibril clumping and interfacial adsorption, alongside emerging solutions to these problems. Furthermore, we examine the complexities of structural polymorphism, discussing how environmental factors and seeding drive conformational diversity and how this heterogeneity impacts biochemical assays. Finally, we highlight the translational value of these high-resolution maps, demonstrating how they enable the rational, structure-based design of peptide inhibitors and small molecules capable of disaggregating pathogenic fibrils.
1. Advancing biological understanding of the poxvirus scaffold through
breakthroughs in cryo-electron microscopy
Jaekyung Hyun and Seu-Na Lee
2. TBD
Salvador Ventura
3. Pursuing the physics of cryoEM image formation
Duane Loh and Joel Yeo
4. AI Tools for Cryo-EM: Protein Particle Picking, Density Map Enhancement,
and Atomic Model Building
Janlin Cheng, Ashwin Dhakal, Rajan Gyawali and Joel Selvaraj
5. Cryo-EM of Amyloid Fibrils: Advances, Challenges, and Translational
Applications
Michal Maj and Dylan Valli
6. TBD
Alex de Marco
7. Computational Approaches for Protein Complex Modeling for Intermediate
Resolution Cryo-EM Maps
Kihara Daisuke
8. Calcium-sensing receptor, involved in the oral perception of the kokumi
substances
Hiroki Yamaguchi and Seiji Kitajima
9. Insights into the Structure and Diversity of the Bacterial Flagellum from
cryo-EM studies
Julien Bergeron, Matias R. Iglesias Rando and Kailin Qin
10. TBD
Toshio Moriya
11. TBD
Brent Nannenga
12. Overview and future potential in structural studies of bacteriophages by
cryo-electron microscopy
Michael Sherman and Elena Orlova
13. TBA
Seth Darst
David B. Teplow, Ph.D., is a Professor of Neurology, Emeritus, at UCLA and an internationally recognized leader in efforts to understand and treat Alzheimer's disease. Dr. Teplow's group has used a multi-disciplinary approach to determine how neurotoxic peptides, such as the amyloid -protein (Alzheimer's disease) and -synuclein (Parkinsons disease), form neurotoxic structures that kill neurons and to develop the means to block these processes. Dr. Teplow received undergraduate training at UC Berkeley; a Ph.D. from the University of Washington; and was a postdoctoral scholar at Caltech. Before coming to UCLA, Dr. Teplow was a faculty member in the Department of Neurology, Harvard Medical School. Dr. Teplow has published >250 peer-reviewed articles, books and book chapters, and commentaries, in addition to serving on numerous national and international scientific advisory boards. Dr. Teplow was a founding editor of the Journal of Molecular Neuroscience and Current Chemical Biology, He is Editor-in-Chief of the Elsevier serial Progress in Molecular Biology and Translational Science and is Associate Editor-in-Chief of the American Journal of Neurodegenerative Disease.
