Deregulation of calcium levels in nerve cells has been linked to early symptoms of Parkinson’s disease. Now, researchers at Aarhus University have found that inhibition of a protein called SERCA can prevent calcium variations and protect nerve cells from degeneration.
This finding may open new therapeutic avenues to treat Parkinson’s motor symptoms, but also non-motor symptoms such as sleep disorders, gastrointestinal problems, anxiety, and depression.
The study, “Alpha‐synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation,” was published in the journal EMBO Reports.
The team showed that in nerve cells with the same type of stress involved in Parkinson’s disease, there is a significant loss of calcium, a basic element in the body without which cells cannot function and eventually die.
The reason behind this observation seems to be the fact that in these cells, α-synuclein aggregates — protein aggregates thought to be behind Parkinson’s development — interact and activate a calcium pump known as the SERCA protein. Interestingly, this process is specific to α-synuclein clumps, as isolated molecules did not interact or activate SERCA.
To further confirm the relevance of these findings, the team analyzed samples of human brain collected from patients affected by dementia with Lewy bodies, characterized by α-synuclein aggregates. They again found the same pattern in which α-synuclein clumps interacted with SERCA and promoted calcium transport outside of the cell.
“The study indicates that the treatment of calcium disturbances is meaningful because the nerve cells are protected. This may help to prevent the disease from developing into such a disabling disease as would otherwise be the case,” Cristine Betzer, PhD, investigator at the brain research centre DANDRITE at Aarhus University and lead author of the study, said in a press release.
By inhibiting SERCA activity with a chemical compound that specifically blocks SERCA in a worm model of Parkinson’s, calcium levels became more stable and cell survival improved. Importantly, inhibition of SERCA protected nerve cells from α-synuclein aggregates’ neurotoxic stress.
“Experiments in the United States with similar models have shown that once the worms with the Parkinson’s protein have lived for eight days, their nerve cells begin to die. In our study, we treated the worms with an inhibitor against the calcium pump and then counted the nerve cells in the worms. And there were many cells left. Which is a sensational and encouraging result,” Betzer said.
Although these findings cannot be directly translated to the human disease they can open new study opportunities that may be useful for the development of new, more efficient therapies.
“Our study points towards the usefulness of treating patients throughout the whole course of the disease, as the calcium pump will otherwise continue to pump and thus contribute to the patient’s symptoms,” Betzer added. “Perhaps the protection of nerve cells can also mean that the damage caused by Parkinson’s disease in the brain does not develop as severely as it otherwise would.”
https://parkinsonsnewstoday.com/2018/05/03/cell-study-provides-hope-treatment-parkinsons-disease/
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