What is LRRK2?

The recent announcement that Sergey Brin, the multibillionaire co-founder of Google, has discovered that he possesses a genetic mutation that predisposes him to a form of Parkinson's disease has resulted in multiple stories in the news on the "genetic basis" of Parkinson's and the candidate gene LRRK2.

But what exactly is LRRK2? The fact that we now have names for so many of these genes signifies one of the true advances in modern medicine - the fact that we actually know the location, but not necessarily the function, of most genes in humans. But we often forget that these genes themselves are very interesting. LRRK2 stands for leucine-rich repeat kinase 2, which means about nothing to most people. This means that the gene encodes for a protein that has within it a leucine-rich regions, and some sort of kinase function. Still mean nothing? Well, leucine-rich regions tend to be associated with proteins that interact with one another. This is common in many metabolic pathways. In fact, we know that the dardarin protein (the protein encoded for by LRRK2) is actively involved in the mitochondria of the cell - the energy powerhouses that burn carbohydrate fuel to produce energy. And the term kinase indicates that this protein is basically a form of cellular "on-off' switch. Kinases add phosphates to other molecules, effectively turning them on or off. So dardarin turns on and off other proteins.

So what does this tell us? Well, by dissecting the name we can see that this gene, and its gene product (the dardarin protein) are most likely a component of a much larger, protein activation pathway. From a cellular perspective, these pathways can be, and usually are, very complex, with defects at many locations possible. Any of these defects may cause Parkinson's. The disease may also be caused by mutations in genes that have nothing to do with dardarin or LRRK2. So, it is unlikely that the discovery of Mr Brin's mutation will be the silver bullet in the fight against Parkinson's disease. Mutations in this gene account for only a small percentage of Parkinson's cases. However, Mr Brin's announcement will serve to increase awareness, and hopefully funding, of research to better understand the chemical pathways that LRRK2 is part of. But we can add dardarin to the diseasome, or those proteins that are known to cause disease. And once we understand the function, we may be able to start talking about gene therapy and drug development.