Protein Mediates Nerve Cells’ Susceptibility to Neurotoxins, Mouse Study Finds

A protein found on the surface of cells mediates nerve cells’ susceptibility to damage and death. This discovery may open new therapeutic avenues to prevent neuron degeneration associated with Parkinson’s disease.

The study, “Targeted deletion of the aquaglyceroporin AQP9 is protective in a mouse model of Parkinson’s disease,” was published in PlosOne. 

Only 10 percent of Parkinson’s disease cases are associated with an inherited genetic cause, and it is still unclear what causes the remaining 90 percent of all sporadic cases. External, environmental toxins are believed to play a role in the development of Parkinson’s disease, but it is not known why dopaminergic neurons are more susceptible to damage.

Previous studies have shown that a protein called AQP9, is present in the dopaminergic neurons of of rats’, mice, and primates’ substantia nigra, which is the brain area affected in Parkinson’s disease and responsible for control movement and coordination.

This particular protein regulates cellular permeability and is an important mediator of cells’ contact with their exterior environment.

University of Oslo researchers evaluated the role of AQP9 in mediating cells’ response to Parkinson’s associated toxins.

They tested AQP9-positive cells’ permeability to MPP⁺ — a neurotoxin known to selectively affect dopamine neurons — and found that MPP⁺ transport was twofold higher in AQP9-positive cells than in any other cell.

To evaluate the role of AQP9 in MPP⁺-mediated toxicity on dopaminergic neurons, the team used brain slices collected from the substantia nigra of mice that had been genetically engineered to lack AQP9. When exposed to the neurotoxin the number of dopamine-producing cells remained roughly the same. In contrast, dopamine producing cells from normal mice died, a response that was prevented upon treatment with an AQP9 inhibitor.

The production of dopamine and dopamine-derived molecules was less affected in mice that did not have the AQP9 protein, suggesting they are, to some extent, protected from MPP⁺‘s harmful effects.

“Our data open for the possibility that toxins and other parkinsonogenic substances access dopaminergic neurons through AQP9,” the researchers stated.

These findings suggest that this surface protein should be explored as a new target for pharmacological intervention.