A possible cure for cataracts

Cataracts are the clouding of the lens in the eye which can lead to blindness or can severely impair sight. Cataracts are most commonly associated with age, but there are about 20 million people on Earth that were born with cataracts. The cause of these congenital cataracts are varied but most suggest that its the crystallin proteins themselves that get mutated. (1) The eye produces these crystallin proteins that are supposed to last a lifetime, so when they are mutated they become unstable and cause cataracts! These are very hard to treat, because its hard to replace crystallin proteins. Recently, a large group of researchers have identified another cause of congenital cataracts - mutations in the gene that creates lanosterol - and they discovered a simple way to treat them! (2)

So what does lanosterol have to do with aggregation of proteins and the cause of cataracts? Lanosterol is the structural precursor to steroids and has little to do with crystallin proteins in the eye. Lanosterol comes from squalene and can be used to form testosterone, estradiol and cholesterol from enzymatic catalysis.

The researchers noticed that a lot of people born with cataracts had some mutations in the genes that help to produce lanosterol in the human body. Obviously then, you might think that increasing lanosterol to compensate for your body’s malfunctioning lanosterol synthetase might help get rid of cataracts…and you would be right! The researchers found that lanosterol can actually significantly decrease protein aggregation of the crystallins in the test tube. The researchers used transmission electron microscopy to show that lanosterol actually dissolved pre-formed amyloid-like fibrils of crystallin proteins - in other words lanosterol can reverse aggregation!

Anyone with cataracts should care, and people that study protein folding diseases should care! Researchers found that simply increasing the dosage of lanosterol could help cataractous rabbits, so it might also work in humans. It’s usually not so simple to solve protein aggregation diseases (like Huntington’s and Alzheimers) because we have no way of reversing the aggregation. This simple addition of lanosterol might be useful in the combat against these other protein folding diseases!

Will lanosterol help reduce aggregation of other amyloid fibrils in other protein folding diseases? How exactly does lanosterol interact with crystallin proteins to de-aggregate them? These, and more questions have yet to be answered, so stay tuned to science!

References

1. Sun, H., et al. “Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans.” Journal of medical genetics 42.9 (2005): 706-710.
2. Zhao, Ling, et al. “Lanosterol reverses protein aggregation in cataracts.” Nature (2015).