Parkinson's disease, like most other neurodegenerative conditions, is characterized not just by chronic inflammation and cell death, but also by protein aggregation. Solid deposits of α-synuclein form in the brain, bringing with them a halo of toxic biochemistry that harms and kills neurons. It is expected that finding ways to clear these aggregates will prove to be an effective treatment for the condition, though there remain questions about the ordering of cause and effect. Does chronic inflammation or mitochondrial dysfunction lead to protein aggregation, or vice versa? As is usually the case, the easiest way to answer these questions is to clear the aggregates in a good disease model, or in the real thing in human patients, and see what happens.
Scientists have investigated the therapeutic potential of GM1 in Parkinson's disease for nearly 30 years. Previous research showed that Parkinson's patients have less GM1 than healthy patients in the part of the brain most affected by Parkinson's, the substantia nigra. Other researchers followed this work to show in cell culture models that GM1 interacts with a protein called alpha-synuclein. In Parkinson's disease, alpha-synuclein can form clumps, which can become toxic to brain cells in the substantia nigra and lead to cell death.
In new work, researchers have shown that giving daily GM1 doses to animals that overproduce alpha-synuclein inhibits the toxic effects of the protein. "When we looked in the brains of these animals, not only did we find we could partially protect their dopamine neurons from the toxic effects of alpha synuclein accumulation, we had some evidence that these animals had smaller and fewer aggregates of alpha-synuclein than animals that received saline injection instead of GM1." In addition to protecting brain cells from death, the treatment also reversed some early motor symptoms.
The researchers suspect that less GM1 in the brains of Parkinson's disease patients may facilitate the aggregation of alpha-synuclein and increase its toxicity. "By increasing GM1 levels in the brains of these patients, it would make sense that we could potentially provide a slowing of that pathological process and a slowing of the disease progression, which is what we found previously in a clinical trial of GM1 in Parkinson's disease patients." The team is now following up on their results to find out what other effects GM1 might have on alpha-synuclein.