Parkinson’s disease, a famous condition after various personalities have been diagnosed with it (such as actor Michael J. Fox, the heavyweight champion Muhammad Ali and the painter Salvador Dalí), may be very near to a cure. A Mexican researcher managed to eliminate its neurological effects with an immunosuppressant.
Gabriela Caraveo Piso, who holds a PhD from Whitehead Institute for Biomedical Research in the United States, discovered that the role of calcium as an intracellular messenger can become lethal to brain cells when there is a high concentration thereof.
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 intracellular calcium rise, leading to over-activation of calcineurin enzyme. This, in turn, removes phosphates (intracellular communication paths) to alter their functions and kill cells.
Gabriela Caraveo, Biologist graduated from the National Autonomous University of Mexico (UNAM), sought to tackle this problem from the root. After performing a series of analyzes in yeast, worms, and mice’s neurons, found that by reducing calcineurin activation levels (without eliminating it completely) the cells survived.
By modifying calcineurin activation, contact with NFAT protein is eliminated and the communication is redirected to cytoskeleton (responsible for cell morphology). Thereby, failure in the motor function in animal models of Parkinson’s was reduced, said Caraveo Piso who works in the lab of Susan Lindquist in the city of Cambridge, Massachusetts.
To achieve adequate toxicity reduction it was used a drug called tacrolimus. This medication is used clinically in newly transplanted patients to prevent organ rejection caused by the immune system.
Calcineurin is also highly expressed in brain, but this immunosuppressant is able to cross the blood brain barrier to reduce calcineurin activation in the brain, decreasing Parkinson’s symptoms. However, it is important to adjust the dosage perfectly, because too much of this drug can eliminate completely calcineurin activation, preventing stimulation of protective pathways like cytoskeleton, leading to cell death. Caraveo Piso explains that the drug’s dosage she is proposing is well below common immunosuppressant’s dosages.
In healthy people, cells are able regulate the amount of intracellular calcium. The problem arises 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, tacrolimus decreased pathologies associated to Parkinson’s disease in rodents. The next step is to start human trials to test its effectiveness and safety as an alternative treatment that may even be the very expected cure to Parkinson’s disease.
Source: Agencia ID