Researchers at Johns Hopkins University found that, LRRK2 gene mutation increases the phosphorylation of ribosomal protein, leading to overproduction of ribosomal proteins, and ultimately the cells to death.
To date, it is unclear in most patients with Parkinson’s disease etiology. But studies show that, LRRK2 mutations are common in this disease. LRRK2 is a kinase phosphorylation, studies have shown that LRRK2 mutations (such as G2019S) will increase the phosphorylation of LRRK2 mediated. Therefore, identification of molecules phosphorylated by LRRK2, Parkinson’s disease can help people understand the neuronal cell death.
The researchers determined that LRRK2 as bait to identify phosphorylation targets. They experiment in human kidney cells, protein components found in the ribosome LRRK2 phosphorylated object.Research shows, LRRK2 pathogenic mutations increase its two ribosomal proteins (s11 and s15) phosphorylation. In addition, carriers of LRRK2 mutations in brain samples, the level of phosphorylation of s15 is higher than the control group.
Subsequently, the researchers rat and human embryonic stem cells into neural cells and carry it through genetic engineering LRRK2 gene mutation. They found that the mutation increases the amount of dead cells and phosphorylated in s15. Studies have shown that if the mutant cell s15 LRRK2 protein mutation, it can not be phosphorylated LRRK2, the cells can be from death.
“This shows, s15 ribosomal protein plays a key role in Parkinson’s disease,” Dr. Dawson said.
Why s15 increased phosphorylation kills nerve cells do? Previous research has shown that if the release of dopamine neurons overexpressing mutant LRRK2 protein, Drosophila nerve cell damage and will dyskinesia appear. Dr. Dawson’s research team discovered that by raising these Drosophila brain s15 phosphorylation levels. And when s15 is not phosphorylated LRRK2, Drosophila cell damage and movement disorders can be restored.
Interestingly, the researchers also found that levels of all proteins in the brains of LRRK2 mutations in fruit flies are abnormally high. This indicates an increase in the phosphorylation s15, ribosome excessive protein synthesis. They used a low dose of anisomycin (drugs can block protein synthesis) processing in Drosophila, succeeded in preventing the nerve cell damage and restore the Drosophila athletic ability, although this time the level of phosphorylation of s15 is still high.
The researchers pointed out that the process of protein synthesis failure, Parkinson’s disease and probably some other root cause of neurodegenerative diseases.