The study, published in the Journal of Biological Chemistry, suggests that the artificial sweetener could be a novel way to reduce the risk of developing Parkinson's and other neurodegenerative diseases because it prevents clumps of the protein alpha-synuclein forming in the brain — a process that is characteristic of Parkinson's disease.
Led by Professors Ehud Gazit and Daniel Segal from Tel Aviv University, Israel, the research team found that mannitol was among the most effective agents in preventing aggregation of the protein in test tubes before testing its ability to block formation in fruit flies and mice.
Gazit and Segal first identified the structural characteristics that lead to the development of clumps of alpha-synuclein, before the team began to hunt for a compound that could inhibit the proteins' ability to bind together.
Then, in order to test the capabilities of the sweetener in the living brain, the team turned to transgenic fruit flies engineered to carry the human gene for alpha-synuclein.
They used a 'climbing assay' test in which the ability of flies to climb the walls of a test tube indicates their locomotive capability. Initially 72% of normal flies were able to climb up the test tube, compared to only 38% of the genetically-altered flies. However when the team then added mannitol to the food of the genetically-altered flies for 27 days and repeated the experiment 70% of the flies could complete the test.
In addition, the team saw a 70% reduction in aggregates of alpha-synuclein in mutated flies that had been fed mannitol, compared to those that had not.
Segal and Gazit noted that these findings in flies were then confirmed in a second study which measured the impact of mannitol on mice engineered to produce human alpha-synuclein. After four months, the researchers found that mice given mannitol also showed a dramatic reduction of alpha-synuclein in the brain.
Segal noted that the benefit of mannitol as a compound to reduce the risk of and possibly even treat Parkinson's is in that it is already approved for use in a variety of foods and for clinical interventions.