Johns Hopkins researchers reveal novel protein and involvement in Parkinson’s disease

Johns Hopkins

Researchers from Johns Hopkins Medical School have highlighted a protein that plays a deleterious role in Parkinson’s disease, as well as deducing the mechanism which may give clues to help understand the disease progression better.

Ted Dawson led the study at Johns Hopkins and with his team published the findings in The Journal of Clinical Investigation.

Parkinson’s disease (PD) is a progressive condition that affects the nervous system and by virtue affects motor movement. The researchers found a protein called c-Abl that was overactive in the autopsied brains of PD patients. They speculated that c-Abl is a driver for the disease. This finding was backed up in a mouse model of PD with a  genetic deletion of c-Abl which effectively reversed the severity of the disease.

"There were indications that c-Abl activity leads to Parkinson's disease, and our experiments show there is indeed a connection," said Dawson in a statement. "There is already a Food and Drug Administration-approved c-Abl inhibiting drug in use for leukemia, so we're interested in whether it could be used safely against Parkinson's disease or as a starting point to develop other treatments."

In a series of experiments, the researchers first genetically removed c-Abl in mice prone to develop PD and observed their disease symptoms reduced in these mice. They then made the gene overactive in the same PD-prone mice showing the reverse was true; the symptoms were worsened because of c-Abl being present in excess. More interestingly, this was also apparent in normal mice not prone to develop PD, which nevertheless developed PD features because of c-Abl’s absence.

Because another protein called α-synuclein has long been known to be involved in PD, the researchers looked at c-Abl’s relationship with α-synuclein. What they observed was increased clumping of α-synuclein when c-Abl was genetically overexpressed--occurring due to the addition of a phosphate group by c-Abl to α-synuclein and making it more likely for α-synuclein to aggregate, making the symptoms worse.

"We plan to look into whether α-synuclein with a phosphate group on the spot c-Abl targets could serve as a measure of Parkinson's disease severity," said Dawson.

Although there is an FDA-approved drug for the treatment of leukemia that targets c-Abl, the authors caution this isn’t yet indicated for PD treatment--and further studies need to be explored before it can be prescribed as a clinical therapy.

- here’s the release

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