Nordic Life Science 1
to waste away. Both effects were reversed when tr
eated with LRRK2-inhibitor drugs. In addition, in mice lacking the gene for LRRK2, protein synthesis was increased in nerve cells. “Our fundamental finding is that LRRK2 influences protein synthesis in cells. In animal models and in skin biopsies from Parkinson’s patients, we detect lower levels of de novo protein synthesis,” says lead author Eleanor Coffey, Research Director, Turku Bioscience Centre, University of Turku and Åbo Akademi University. To better understand how LRRK2 reduces protein synthesis, the scientists examined the substantia nigra region of the brain, which is affected in Parkinson’s disease. In rats exposed to rotenone, they found that controllers of protein synthesis acquired “phosphate marks” that signal protein synthesis to stop. One such mark was particularly prominent in patient skin cells. LRRK2-inhibitor drug reversed these marks and allowed the cell to resume making new proteins. “It is significant that we found no evidence of decreased protein synthesis in individuals with multiple system atrophy, a movement disorder that is symptomatically difficult to distinguish from Parkinson’s disease, but has a distinct etiology and prognosis,” says Coffey. This suggests that a reduction in the synthesis of certain proteins are specific to Parkinson’s disease and could be used as a biomarker readout. “Currently there are no simple tests, such as a blood test, available to detect Parkinson’s disease. According to Current Care Guidelines, diagnosis is based on clinical neurological examination using a scoring system where at least two typical symptoms should be identified and all atypical symptoms must be excluded. Diagnosis typically can take a long time and by the time patients experience motor symptoms, the disease is at an advanced stage. Brain imaging such as PET or DaTScan can be used to help exclude other diseases. However these are invasive approaches that require costly infrastructure and clinical expertise. Brain imaging is not practical for early stage screening, for example,” explains Coffey. As patients aged and the disease progressed, the repression of protein synthesis was also more notable. This did not happen in healthy individuals. Analyzing the repression of the synthesis of certain proteins will provide a means to monitor disease progression, state the researchers. “We are now identifying specifically which proteins are most affected in patient samples and compiling a “signature” of proteins that best distinguish Parkinson’s disease,” says Coffey. NLS 76 Eleanor Coffey and her research group at the Turku Bioscience Center