Suppressing Mitochondrial Fission as a Potential Treatment for Parkinson's Disease
Mitochondria are bacteria-like organelles that swarm in their thousands in each of our cells, and they are important in aging because they can suffer forms of damage that negatively impact the functionality of their host cell. The mitochondrial population of any given cell is very dynamic: they swap protein machinery, fuse with one another, divide like bacteria, and are destroyed by cellular quality control mechanisms. Cells can even transfer mitochondria between one another, and all this takes place constantly at a very rapid pace. It has made it very challenging to prove exactly how damage to mitochondria occurs and propagates, which is one of the reasons why the SENS rejuvenation research approach is to jump over that question and focus on repair strategies that will work no matter how the damage is caused and spreads.
Mitochondrial dysfunction leading to higher rates of cell death or malfunction is implicated in a variety of specific age-related conditions, Parkinson's disease among them, and for reasons that may or may not run in parallel to the damage of aging. This has placed a spotlight on mitochondrial dynamics and the ability to manipulate their activities, as here. It is interesting to speculate on why less fission is beneficial; perhaps it allows mitochondrial quality control processes more chances to destroy damaged mitochondria before they replicate, or perhaps an increase in the rate of fusion over fission allows for more of the mitochondria in a cell to have all of the necessary proteins for complete function rather than just a damaged set:
The inhibition of a particular mitochondrial fission protein could hold the key to potential treatment for Parkinson's Disease (PD). The debilitating movement symptoms of the disease are primarily caused by the death of a type of brain cell that produces a chemical called dopamine. Understanding why these nerve cells die or do not work properly could lead to new therapies for PD.Mitochondria are small structures within nerve cells that help keep the cells healthy and working properly - they are, in effect, the power generators of the cell. Mitochondria undergo frequent changes in shape, size, number and location either through mitochondrial fission (which leads to multiple, smaller mitochondria) or mitochondrial fusion (resulting in larger mitochondria). These processes are controlled mainly by their respective mitochondrial fission and fusion proteins. A balance of mitochondrial fission/fusion is critical to cell function and viability.
The research team found that when a particular mitochondrial fission protein (GTPase dynamin-related protein-1 - Drp1) was blocked using either gene-therapy or a chemical approach in experimental models of PD in mice, it reduced both cell death and the deficits in dopamine release - effectively reversing the PD process. The results suggest that finding a strategy to inhibit Drp1 could be a potential treatment for PD.