Experimental Therapies for Parkinson's Disease

Cells depend on Parkin to help get rid of damaged mitochondria. But in some studies, parkin depends on other proteins, including one called MITOL that has not previously been linked to Parkinson’s disease, to direct it to those damaged mitochondria. The finding might help improve experimental therapies for Parkinson’s that aim to boost Parkin activity.

Researchers at Tokyo Metropolitan Institute of Medical Sciences are reporting; new insight into how the Parkinson’s disease associated protein Parkin selects its targets. Parkin is attracting to damaged mitochondria; where it adds a degradation tag called ubiquitin to proteins on the mitochondrial surface.

Lysine-Containing Protein With Ubiquitin

But in some patients with familial Parkinson’s disease;But in some Parkin activity is disrupted and bad mitochondria cannot be destroyed. Harmful by products from those bad mitochondria can damage neurons. But by understanding how Parkin works and what goes wrong when it’s mutated; researchers hope to help patients with other forms of Parkinson’s disease, too.

While studying how Parkin chooses its substrates; Matsuda’s lab at the Tokyo Metropolitan Institute of Medical Science discovered that; Parkin can tag any lysine-containing protein with ubiquitin even a bacterial protein ;But this is not ordinarily found in the cell; if it’s present at the surface of the mitochondria. 

Parkin is attracting to damaged mitochondria; where it adds a degradation tag called ubiquitin to proteins on the mitochondrial surface.But Parkin can tag any lysine-containing protein with ubiquitin even a bacterial protein ;where it adds a degradation tag called ubiquitin to proteins on the mitochondrial surface.

Ubiquitin Is Adding By A Protein 

The discovery that activated Parkin is not terribly selective led Koyano and her colleagues to take a closer look at Parkin’s recruitment and activation. Some detailing on that processing are well knowing; But for example, a protein called PINK1 is knowing to boost Parkin activity. But Koyano and colleagues discovered a new step that must happen before PINK1 can contribute to Parkin activation.

By this study found that Parkin acts much more rapidly when a first ubiquitin molecule is already present; acting as a “seed” for addition of more ubiquitins. In most cases, the researchers found; this seed ubiquitin is adding by a protein called MITOL; which is not previously have been linking to Parkinson’s disease.

But this research could help contribute to drug-design initiatives, some of which aim to boost Parkin activity to slow the advance of Parkinson’s disease; it might accelerate Parkin recruitment and Parkin activation to eliminate damaged mitochondria more efficiently.