Boosting Levels of Molecule in Brain Slows Parkinson’s Progression and Eases Symptoms, Animal Study Finds

Catarina Silva, MSc avatar

by Catarina Silva, MSc |

Share this article:

Share article via email
antibodies and alpha-synuclein

A molecule called GM1 ganglioside may protect the brain against the molecular changes associated with Parkinson’s disease progression, and may one day directly treat its neurodegenerative processes, according to an early study.

The study, “GM1 Ganglioside Modifies α-Synuclein Toxicity and is Neuroprotective in a Rat α-Synuclein Model of Parkinson’s Disease,” was published in Scientific Reports.

GM1 ganglioside is a component of the cell membrane and has long been considered a master modulator of the nervous system because of the many functions it regulates.

Parkinson’s patients have lower-than-usual levels of GM1 ganglioside within the substantia nigra, a brain region that’s severely damaged in Parkinson’s.

In lab experiments, GM1 ganglioside was found to protect against the aggregation of alpha-synuclein protein, the main component of Parkinson’s hallmark Lewy bodies. Specifically, GM1 ganglioside did not allow acetylated alpha-synuclein to form harmful clumps or aggregates within the cells. Acetylated (with an added acetyl group) alpha-synuclein has been shown to more effectively induce intracellular clustering in nerve cells, compared to the unchanged form of alpha-synuclein.

This suggests that problems with GM1 may somehow contribute to the vulnerability and degeneration of dopamine-producing neurons seen in Parkinson’s disease.

Using a rat model of Parkinson’s, researchers for this study investigated the extent to which GM1 ganglioside could protect against alpha-synuclein toxicity and the development of Parkinson’s-related molecular and behavioral changes.

A single injection of an adeno-associated viral vector (AAV) carrying a copy of human mutant alpha-synuclein was administered into the substantia nigra of rats, leading to protein aggregation and the degeneration of dopaminergic neurons, a decrease in dopamine levels within the striatum (another motor control brain center that’s affected by Parkinson’s), and behavioral problems.

Some rats were then randomly assigned to daily GM1 ganglioside injections (30 mg/kg) beginning 24 hours after AAV-alpha-synuclein administration and lasting for six weeks (early start group). Others were given the daily GM1 ganglioside injections (30 mg/kg) three weeks after the AAV-alpha-synuclein, and lasting for five weeks (delayed start group).

Results showed that GM1 ganglioside protected against loss of substantia nigra dopamine-releasing neurons and striatal dopamine levels, and reduced alpha-synuclein clumping. Importantly, the delayed start of GM1 ganglioside reversed motor deficits that had appeared in this animal group, suggesting the therapy was able to restore their motor function.

“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,” Jay Schneider, PhD, a professor in the department of pathology, anatomy and cell biology at Thomas Jefferson University and first author of the study, said in a press release.

Scientists believe the low brain levels of GM1 ganglioside seen in Parkinson’s may facilitate the formation of harmful alpha-synuclein clumps.

“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,” Schneider said. Results of that university-sponsored trial (NCT00037830) in 77 patients, concluded in 2010, supported its potential as a disease-modifying treatment.

Schneider’s team is now focused on finding out what other effects GM1 ganglioside might have on alpha-synuclein.

“It’s important to understand how GM1 is working because there might be other ways we could manipulate GM1 levels in the brain to have a beneficial effect,” he added.

According to the researchers, GM1 has the potential to be a treatment that directly impacts “the underlying disease processes in [Parkinson’s disease] and that can slow neuronal cell death and symptom progression,” protecting dopamine neurons from dying “as well as rescue and restore function to damaged but viable neurons.”

Your Parkinson’s Community

Woman laying down illustration

Visit the Parkinson’s News Today forums to connect with others in the Parkinson’s community.

View Forums