Parkinson's disease, which took world fame after being diagnosed in various personalities such as actor Michael J. Fox, the heavyweight champion Muhammad Ali and the painter Salvador Dalí, could be very close to a cure, thanks to a Mexican researcher which managed to eliminate its neurological effects with an immunosuppressant.
Responsible for the scientific finding is Gabriela Caraveo Piso, researcher at the Whitehead Institute for Biomedical Research in the United States, who discovered that the role of calcium as an intracellular messenger can become lethal to brain cells when in high concentration.
Neurological diseases called synucleinopathies, such as Parkinson's, are characterized by the aggregation of alpha-synuclein protein. This action triggers a series of events such as the rise in intracellular calcium leading to over-activation of the enzyme calcineuria. This in turn removes phosphates (intracellular communication paths) to alter their functions and kill cells.
Gabriela Caraveo, a biologist graduated from the National Autonomous University of Mexico (UNAM), sought to nip this problem, after performing a series of analyzes in yeast, worms, and neurons of mice, found that by reducing the levels of activation of calcineurin, without eliminating it completely, the cells survived.
By modifying the activation of calcineurin contact with NFAT protein is cut out, and the communication to actin cytoskeletal rearrangements is redirected, which is responsible for cell morphology, thereby reducing failure in the motor function in animal models of Parkinson said the Mexican, who works in the lab of Susan Lindquist in the city of Cambridge, Massachusetts
To achieve adequate toxicity reduction the drug tacrolimus was used, which is administered clinically in newly transplanted patients to prevent organ rejection by the immune system.
Because calcineurin is also highly expressed in brain, this immunosuppressant that can cross the blood brain barrier is able to reduce the activation of calcineurin in the brain reducing the toxic symptoms of the disease. But it is important to adjust the dosage, because too much of it completely eliminates the activation of calcineurin preventing stimulation of protective pathways like the cytoskeleton leading to cell death.
"The dosage of the drug, also called FK506, I propose is well below the level of the immunosuppressants, which allows my work to have immediate treatment of neurological diseases characterized by the aggregation of alpha-synuclein as therapeutic implications as the Parkinson's disease," explained the specialist in neurosciences.
In healthy people, cells achieve to regulate the amount of intracellular calcium, the problem is when there are neurological diseases such as Parkinson's disease, the element is accumulated, becomes toxic and kills many neurons including dopaminergic neurons, responsible for implementing the motor functions.
According to preclinical results with tacrolimus pathologies associated to Parkinson's disease decreased in rodent models. The next step is to start human trials to test its effectiveness and safety as an alternative treatment that could even act as a cure.
Whitehead Institute for Biomedical Research