Background
There is lots of evidence that the energy hub of the cell, the mitochondria, is damaged in Parkinson’s Disease (PD) and that this damage contributes to the death of specific brain cells. There are several ways in which damage to mitochondria is thought to contribute to PD and preventing this damage might be beneficial in developing future treatments.
Why is the study important?
This study highlights a natural product, Cordycepin, isolated from the fungus Cordyceps militaris, which has protective effects in an animal model of PD. The study further identifies that Cordycepin protects several functions related to the mitochondria. Although Cordycepin itself requires much more investigation to determine if it is safe and could be beneficial to PD patients, the study highlights that Cordycepin may prevent brain cell damage. This provides evidence for future studies to investigate similar types of molecules as a potential therapy for PD.
What did the authors do and how did they do it?
The authors of this study investigated the effect of Cordycepin on both rats and brain cells isolated from rats treated with a toxin, known as rotenone, which mimics some of the features of Parkinson’s Disease. To do this, the rats and isolated brain cells were treated with the toxin either on its own or with varying amounts of Cordycepin and several indicators of physical, cell and mitochondrial health were measured.
What are the results?
Firstly, animals were tested for their ability to move, which is impaired by the toxin rotenone. Rats treated with Cordycepin moved more and were better able to run on a rotating rod, indicating that Cordycepin protected the rats from the effect of the toxin on their movement. The toxin also causes cell death in the area of the brain affected by PD and Cordycepin provided significant protection against this.
The authors next investigated how Cordycepin affected the mitochondria. When mitochondria are damaged by the toxin rotenone, they not only produce less energy for the cell but can also produce toxic molecules, known as reactive oxygen species. Less energy and toxic molecules are both thought to contribute to the cell death which leads to symptoms in Parkinson’s Disease. Cordycepin decreased the production of toxic molecules, and increased the amount of energy, produced by the mitochondria.
In healthy cells, mitochondria can fuse together (fusion) or divide into two (fission) to maintain their complex networks. Cordycepin was found to partially restore the balance of molecules needed for these processes, which are damaged by the toxin rotenone. Finally, Cordycepin was found to reduce the inflammatory response which is induced by the mitochondria when treated with the toxin rotenone. The inflammatory response is thought to begin as a protective mechanism in Parkinson’s Disease which eventually becomes detrimental to the cells. Therefore, reduction of the inflammatory response may be beneficial in slowing the progress of Parkinson’s Disease.
What do the findings mean going forward for people with the disease?
These findings identify a small, natural product that can, when injected directly into the brain of rats, alter some of the damage that is thought to contribute to Parkinson’s Disease. Future studies are likely to assess whether Cordycepin can enter the human brain and how it is broken down by the human body. These studies are also likely to test whether Cordycepin is protective against the other symptoms of PD that were not tested in this study. Finally, the findings of this study could inform the development of similar molecules which protect against damage in PD.