Researchers have discovered how a protein linked to Parkinson's disease may protect cells such as neurons in the brain. The study revealed how a protein called Parkin - which is lost in certain forms of Parkinson's disease - 'buys time' for cells to repair internal damage that may otherwise kill them.
The discovery could underpin the development of new therapies that slow the progression of Parkinson's disease by saving cells that would otherwise die. The research was published in The EMBO Journal.
"In a healthy brain, Parkin helps keep cells alive, and decreases the risk of harmful inflammation by repairing damage to mitochondria, which are responsible for supplying energy to cells.," the graduate student said.
The author said damaged mitochondria could trigger the cell's internal death machinery, which removed unwanted cells by a cell death process termed 'apoptosis'.
"We discovered that Parkin blocks cell death by inhibiting a protein called BAK.
"BAK and a related protein called BAX are activated in response to cell damage, and begin the process of destroying the cell - by dismantling mitochondria. This ultimately drives the cell to die, but low-level mitochondrial damage has the potential to trigger inflammation - warning nearby cells that there is potential danger," the author said.
The team showed that Parkin restrains BAK's activity when mitochondria are damaged. Parkin tags BAK with a tiny protein called Ubiquitin.
The senior author said Ubiquitin was a 'go slow' signal for BAK. "With normal Parkin, BAK is tagged and cell death is delayed. Parkin 'buys time' for the cell, allowing the cell's innate repair mechanisms to respond to the damage," the senior author said.
"Without Parkin - or with faulty variants of Parkin that are found in patients with early-onset Parkinson's disease - BAK is not tagged and excessive cell death can occur. This unrestrained cell death may contribute to the neuronal loss in Parkinson's disease.
By understanding how cell death and inflammation occur in Parkinson's disease, the researchers hope new therapies may be developed that could slow the progression of the disease.
"Drugs that can stifle BAK, mimicking the effect of Parkin, may have the potential to reduce harmful cell death in the brain," the senior author said.
Parkin delays cell death by targeting death protein!
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