Dopamine-releasing neurons in a region of the brain called the substantia nigra lead a lifestyle that requires lots of energy, creating stress that could lead to the neurons' premature death, which causes Parkinson's disease, Northwestern Medicine scientists have discovered.
"Why this small group of neurons dies in Parkinson's disease is the core question we struggled with," said lead author D. James Surmeier.
"Our research provides a potential answer by showing this small group of neurons uses a metabolically expensive strategy to do its job. This 'lifestyle' choice stresses the neurons' mitochondria and elevates the production of superoxide and free radicals - molecules closely linked to aging, cellular dysfunction and death," Surmeier said.
The good news is preclinical research shows this stress can be controlled with a drug already approved for human use.
By preventing calcium entry, the drug isradipine reduced the mitochondrial stress in dopamine-releasing neurons to the levels seen in neurons not affected by the disease.
Researchers are currently conducting a clinical trial to find out if isradipine can be used safely and is tolerated by patients with Parkinson's.
Isradipine is already approved by the Food and Drug Administration for treatment of high blood pressure.
The symptoms of Parkinson's disease include rigidity, slowness of movement and tremors. No treatment currently is known to prevent or slow the progression of Parkinson's disease.
The study has been published Nov. 10 in the journal Nature.