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Cryo-EM Drives Advances in Parkinson’s Disease Research

By 09.23.2020

Parkinson’s disease is a debilitating disorder that continues to impact millions, but there is still little known about the underlying mechanisms of the disease. However, recent work from the University of California San Diego has revealed critical details regarding a key protein linked to genetically inherited Parkinson’s disease, the leucine-rich repeat kinase 2 (LRRK2). While its ties to Parkinson’s have been known since the early 2000s, the mechanism and structure of LRRK2 have evaded researchers. Now, using both cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), scientists from the Reck-Peterson, Leschziner, and Villa groups of UCSD were able to visualize the protein, both at high resolution and within its natural cellular environment. Future drugs designed to combat Parkinson’s would rely on this kind of fundamental information, including LRRK2’s structure, behavior, and function within the cell, to be effective.

LRRK2 protein model showing how it could block critical movement across the cell

Roadblock: This image depicts a model for how LRRK2 could block critical movement across the cell. The visualization shows a short LRRK2 filament (red, green and yellow) wrapped around a cellular track called a microtubule, forming a roadblock for the microtubule-based motors kinesin (light blue) and dynein (blue). (Photo credit: Leschziner Lab, UC San Diego)

Cryo EM and the Aligning Science Across Parkinson’s initiative

This work has prompted substantial investment from the Aligning Science Across Parkinson’s (ASAP) initiative, which has extended a $7.2 million grant to these laboratories, along with two others based in Germany. This funding, as well as the publication of these results in both Nature and Cell, underscores the vital importance of cryo-EM techniques for further expanding our general understanding of Parkinson’s disease pathology.

Thermo Fisher Scientific is honored to support this critical work through our cryo-EM instrumentation, and we look forward to seeing the future advances these groups make in the battle against Parkinson’s and other diseases.

To learn more about our cryo-EM instruments, please see our life sciences microscopy webpage.

Bernhard Goetze is director, product marketing at Thermo Fisher Scientific.

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