Protecting crucial brain cells from too much calcium

Neuroprotection in MPTP-treated mice by conditional ablation of the mitochondrial calcium uniporter

George Robertson
Dalhousie University
Pilot Project Grant
$50,000 over 1 year

Within the last decade, researchers discovered that people taking drugs that block calcium channels to treat high blood pressure enjoy a lower risk of developing Parkinson’s disease.

This serendipitous discovery opened an avenue of research into the relationship between calcium and mitochondria—tiny components within cells that convert oxygen and sugar into energy. Mitochondria need calcium to stimulate this process.

At Dalhousie University, Professor George Robertson is developing a mouse model to study the MCU (mitochondrial calcium uniporter), a protein that moves calcium into mitochondria. Too much mitochondrial calcium triggers cell death—including the dopamine-producing brain cells that are key to Parkinson’s disease.

After developing a mouse that lacks the MCU in dopamine cells, Robertson and his team will expose these mice to a toxin that produces Parkinson’s symptoms in animals and people. If these MCU-deficient mice are protected, it will validate this protein as a drug target for Parkinson’s disease.

“We’re going to see if knocking out the MCU protects mice from a toxin that causes Parkinson’s disease,” Robertson says. “The idea is that blocking the MCU will reduce the death of vulnerable dopamine neurons in Parkinson’s disease.”

If Robertson’s research is successful, it would encourage the development of drugs that block the MCU in dopamine neurons.

Since most people have already lost about 80 percent of their dopamine-producing brain cells by the time they are diagnosed with Parkinson’s, this approach would not reverse the disease. If successful, it could slow disease progression by preventing further cell death, giving people a better quality of life for longer.

“If we can show what we have predicted … it would encourage chemists to make a compound that gets into the brain to reduce the rate of decline of Parkinson’s disease,” says Robertson.

Robertson, whose doctor and grandfather were both physicians, was inspired to pursue a career in medical research after watching an interview with Swedish scientist Anders Björklund on CBC’s Take 30 television show in 1980. Björklund pioneered the use of transplanting brain cells to try to treat Parkinson’s.

“The interview was so well done it left a lasting impression on me,” says Robertson.

When given the opportunity to work in Parkinson’s disease, Robertson was immediately interested. Today he hopes his ongoing research into different ways to suppress the MCU protein will pay off for people with Parkinson’s.

“I think it’s (MCU) a fundamental mechanism for cell death in dopamine neurons, and it feels right to me in terms of its importance and how things are coming together,” Robertson says. “The challenge is finding a way to target it selectively and safely in people.”