In pursuit of a Parkinson's cure,
we set our standards higher than ever before.
Literally.
On Monday, August 14th at 12:31 PM EDT the SpaceX CRS-12 mission launched from Kennedy Space Center carrying over 20 different scientific experiments to the International Space Station. One of the experiments being sent to the ISS on this mission is the microgravity crystallization of the LRRK2 protein in the Microlytic Crystal Former. This research is a collaboration between The Michael J. Fox Foundation, the Center for the Advancement of Science in Space (CASIS), The University of Oxford, Goethe-University Frankfurt, and the University of California, San Diego.
Parkinson’s Disease is a chronic and progressive neurodegenerative disorder that affects over one million people in the United States and over five million people worldwide(1). Patients with Parkinson’s experience a number of motor symptoms including trembling in the hands, arms, legs and face; stiffness of the limbs and trunk; slowness of movement (bradykinesia), and impaired balance. Non-motor symptoms, such as cognitive deficits and depression can also be present as well(2). Although there are medications for the symptoms of Parkinson’s, there are currently no treatments that reverse or eradicate the disease.
One promising drug target for the treatment of Parkinson’s Disease is LRRK2 (leucine-rich repeat kinase 2)(3). Mutations in the gene encoding the LRRK2 protein are among the most common genetic causes of Parkinson’s Disease(4). LRRK2 is a large (286 kDa), multi-domain protein with both GTPase and kinase functions(5), and the majority of the disease-causing mutations occur within these two domains(6). To date, the structure of LRRK2 has not been determined; however, a model of the full length protein was constructed in 2016(7).
The goal of this experiment on the International Space Station is to improve the resolution of LRRK2 protein crystals. Microgravity protein crystallization has been shown to improve the quality of protein crystals in several ways, including size, mosaicity, and diffraction quality(8, 9, 10, 11, 12, 13. 14). This can help scientists study the structure of LRRK2 and develop optimized therapies against this target. The microgravity crystallization experiments of the LRRK2 protein are being performed in the Microlytic Crystal Former 16-Channel Chips. The Crystal Former utilizes the method of free-interface diffusion to increase crystallization hit rates in an easy to use and efficient manner(15).
The Michael J. Fox Foundation
The Michael J. Fox foundation is dedicated to finding a cure to Parkinson’s Disease, and has raised over 700 million dollars towards that goal since 2000. To learn more about the foundation, and find out how you can help, visit the MJF Foundation website.
Upcoming Meetings
Anatrace is sponsoring the 10th General Meeting of the International Proteolysis Society in Banff, Canada (Oct. 28 – Nov. 2) and will be attending the Fifth GPCR Workshop in Kona, Hawaii (Dec 5-9). Stay up to date on all of the conferences Anatrace will be attending by visiting our Events Calendar.

References:
- Parkinson’s Disease Foundation.
- NIH NINDS Parkinson’s Information Page.
- Taymans, J. M. and Greggio, E. (2016) Curr Neuropharmacol. 14(3), 214-225.
- Manzoni, C. (2017) Biochem Soc Trans. 45(1), 155-162.
- Wallings, R., et al. (2015) FEBS J. 282(15), 2806-2826.
- Resenbusch, K. E. and Kortholt, A. (2016) Parkinsons Dis.: doi: 10.1155/2016/7351985. Epub 2016 May 12.
- Guaitoli, G., et al. (2016) Proc Natl Acad Sci U S A 113(30): E4357-66. doi: 10.1073/pnas.1523708113. Epub 2016 Jun 29.
- McPherson, A. and DeLucas, L. J. (2015) NPJ Microgravity: doi: 10.1038/npjmgrav.2015.10. eCollection 2015.
- Owens, G. E., et al. (2016) Acta Crystallogr F Struct Biol Commun. 72(Pt 10), 762-771.
- Carruthers, C. W., Jr, et al. (2013) PLoS One 8(11): e82298. doi: 10.1371/journal.pone.0082298. eCollection 2013.
- Safonova, T. N., et al. (2012) Acta Crystallogr Sect F Struct Biol Cryst Commun. 68(Pt 11)m 1387-1389.
- Day, J. and McPherson, A. (1992) Protein Sci. 1(10), 1254-1268.
- Ng, J. D. (2002) Ann N Y Acad Sci. 974, 598-609.
- DeLucas, L. J., et al. (1999) Gravit Space Biol Bull. 12(2), 39-45.
- Stojanoff, V., et al. (2011) Acta Crystallogr Sect F Struct Biol Cryst Commun. 67(Pt 8), 971-975.