Researchers at the University of Illinois have discovered a previously unknown genetic risk factor for Parkinsons disease. And because its an18-14g deletion it means it stands to be of benefit to patients with the rare often fatal disease.
The researchers reported experiments with mice expressing the familial neurodegeneration tau protein which causes the onset of a clinical form of Parkinsons disease. They also showed that mutant forms of this protein tend to accumulate in brain cells of animal models of Parkinsons.
The findings suggest that these mutant forms of this protein may be a cause for Parkinsons disease suggesting a new direction for future research.
Im excited because there are no other mutations known to be capable of creating antibodies that specifically target this protein. If we ultimately develop a drug perhaps this could the most appropriate target in the pathogenesis of Parkinsons Joseph Firth professor of biochemistry and biophysics at the U. of I. said Sundasay Nadyadyan a findings scholar at UIC.
Parkinsons disease is a complex neurodegenerative disorder that affects approximately 1 of the U. S. population. In some cases patients may experience memory loss motor symptoms muscle stiffness tremors and sometimes stomach pain as well as speech and language impairment. A neuropathological study in 99 of patients showing both hypermutated and mutated forms of the gene are very difficult to detect due to the lack of high-quality samples and brain tissue.
We want to understand the pathogenesis of Parkinsons disease in a natural patient- and even population specific manner Nadyan said. And our mechanism of molecular targets has so far shown that activated brain stem cells have higher expression of the mutant form potentially resulting in a more causal role of the mutant form in the pathogenesis of Parkinsons disease.
New data from the research team published in Cell Reports showed that SF3B1 plays a crucial role in the regulation of the phosphorylation level of the SF1 pre-synaptic protein RpoA in PD-receptor cells. This mechanism regulates expression of L-type calcium channel (LCCs) and is essential for proper neuronal differentiation. This common mutation in the SF1 pre-synaptic protein RpoA produced by our study subjects leads to a loss of phosphorylation of this gene Nadyan said. Our study suggests that this effect on SF1 pre-synaptic protein RpoA regulation may be a new cause of Parkinsons disease.
In addition to Nadyan study authors include first authors Kendi Atomi Michelle Campbell and Mikhail Arshinin as well as co-author Elisa Sacco.
Although these studies are impressive and demonstrated researth(. . . )that we can developt strategies that will be able to stop the disease process our designs dont exclude the possibility of a future clinical study. At the same time it seems nearly impossible to make progress in the immunotherapy of Parkinsons disease with biologics given the current success with drugs that target only these mutations.