Two New Studies Shed Light On Parkinson’s Disease Cause
Parkinson’s disease is one of the most common nervous system disorders of the elderly, but the root cause of the disorder remains a mystery. Two separate research groups have found new evidence which may help lead to a better understanding of why people develop Parkinson’s and how it might eventually be cured.
Parkinson’s disease occurs when the nerve cells in the brain that make dopamine, a brain chemical that controls muscle movement, are slowly destroyed. When 80% of these cells die or become damaged, symptoms begin to appear, which include tremors, slowness of movement, rigidity, and difficulty with balance. The damage and loss of muscle function worsens over time and, if left untreated, can lead to a deterioration of all brain functions.
While the cause of Parkinson’s was obvious (destruction of dopamine-making cells), the trigger of the damage remained unclear. Investigators from Saint Louis University have found evidence that a toxin produced by the brain, called DOPAL, a breakdown product of dopamine, plays a key role in destroying the dopamine neurons.
DOPAL also appears to be involved in the aggregation of a protein called alpha-synuclein seen in patients with Parkinson’s disease. This further increases the destruction of dopamine-producing cells.
Lead researcher W. Michael Panneton PhD, a professor of pharmacological and physiological science at Saint Louis University School of Medicine, believes the findings could lead to research avenues that could hopefully prevent dopamine neuron loss and slow or halt the progression of Parkinson’s disease.
In another study, conducted at Emory University School of Medicine, researchers have found that a protein called MEF2D, which helps the brain cells withstand stress and toxins, plays a role inside the mitochondria of the cell. MEF2D binds one particular mitochondrial gene, ND6, which is necessary for the assembly of Complex I – a necessary component of the electron transport process.
In Parkinson’s disease, even when MEF2D levels are increased in the cell as a whole, they are reduced in the mitochondria. This disruption leads not only to neurodegenerative diseases, but also may contribute to heart disease.
"Our data suggest that problems with MEF2D in mitochondria could represent one of the earlier steps in the progress of the disease," says senior author Zixu Mao, PhD, associate professor of pharmacology and neurology at Emory University School of Medicine.
Panneton WM, Kumar VB, Gan Q, Burke WJ, Galvin JE, 2010 The Neurotoxicity of DOPAL: Behavioral and Stereological Evidence for Its Role in Parkinson Disease Pathogenesis. PLoS ONE 5(12): e15251. doi:10.1371/journal.pone.0015251
H. She, Q. Yang, K. Shepherd, Y. Smith, G. Miller, C. Testa and Z. Mao. Direct regulation of complex I by mitochondrial MEF2D is disrupted in a mouse model of Parkinson disease and in human patients. J. Clin. Invest.