Parkinson’s disease is a neurodegenerative disorder characterized by slowed or impaired movement, tremors, and a general loss of motor control. Affecting millions of people worldwide, the disease is still without a cure; however, new research from Gabriela Caraveo Piso at the Whitehead Institute provides real hope that a cure for Parkinson’s disease is within reach.
On a molecular level, Parkinson’s disease is characterized by the formation of what are called Lewy Bodies, which can be seen as the larger dark spots in the image below. One of the major components of Lewy Bodies is a clumping of alpha-synuclein (α-syn) protein that is toxic to the surrounding cells. Normally, α-syn is important for communication between nervous system cells called neurons, but when α-syn clumps together in Lewy Bodies, it becomes neurotoxic. This situation impairs cell communication and eventually leads to cell death and neurodegeneration.
Image Source: Visuals Unlimited, Inc./Carol & Mike Werner
Research on α-syn has shown that one of the consequences of the accumulation of α-syn is a rise in the intracellular levels of calcium. This, in turn, over-stimulates a corresponding enzyme called calcineurin, which disrupts cell communication, leading to cell death. In her research, Dr. Caraveo Piso sought to find a way to reduce the activity of calcineurin in hopes of preventing cell death. Normally, the body’s cells are able to regulate calcium levels, but in diseases like Parkinson’s, deregulation of cellular calcium levels leads to neuron damage. An example of neurons that are damaged in Parkinson’s disease are those that regulate levels of dopamine, a neurotransmitter that communicates cellular messages necessary for proper motor function. This would explain the impaired movements of those with Parkinson’s disease.
Dr. Caraveo Piso tested the effect of an immunosuppressant called tacrolimus on yeast, worm, and mice neurons, discovering that small dosages of tacrolimus reduced the activity of the calcineurin enzymes and subsequently prevented cells from dying. Traditionally, tacrolimus is used to ensure that the immune systems of patients receiving new organs do not reject the newly implanted organ.
Image Source: Sherbrooke Connectivity Imaging Lab (SCIL)
Tacrolimus is able to cross the blood-brain barrier, a membrane separating circulating blood from the brain’s fluid cushion that regulates what comes in contact with the brain, and reduce the brain’s activation of calcineurin. The reduced activation of calcineurin enzyme results in the reduction of the symptoms of Parkinson’s disease. Animal models of Parkinson’s disease that were treated with tacrolimus had reduced motor impairment, a promising sign that this treatment could slow or even prevent the major symptoms of Parkinson’s in humans.
The next step for these developments is human trials to test for safety and effectiveness in human cases of Parkinson’s disease, but early experiments on mice models are promising signs that life-changing treatments for Parkinson’s are just on the horizon.
Feature Image Source: Pensive Parent by Jeremy Atkinson
