A molecule reduces the accumulation of toxic proteins in the Parkinson's disease model

Parkinson's disease often starts with small tremors. Over time, the symptoms worsen. The tremors become tremors and the stiffness takes the body hostage. People at advanced stages of neurodegenerative disease often have problems with coordination, walking and maintaining balance. Currently, there is no cure for the disease and the available treatments only treat the symptoms. No treatment can slow the progression of the disease.

Now an international team of researchers led by Jay Schneider, Ph.D., professor in the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, publishes new information that may partly explain how a molecule called ganglioside GM1 protects the brain against the main features of Parkinson's disease. The discovery also indicates that GM1 is one of the first potential treatments to directly affect the degenerative processes that cause the disease.

Dr. Schneider has been studying the therapeutic potential of GM1 in Parkinson's disease for almost 30 years. In previous research, he and his colleagues showed that patients with Parkinson's disease had less GM1 than healthy patients in the part of the brain most affected by Parkinson's disease, called substantia nigra. Other researchers have 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 that can become toxic to the brain cells of the substantia nigra and lead to cell death. "The aggregation of alpha-synuclein aggregates has been proposed as one of the major pathological processes of Parkinson's disease," Dr. Schneider said.

In their new work, Dr. Schneider and colleagues have shown that administering daily doses of GM1 to animals overproducing alpha-synuclein inhibits the toxic effects of the protein.

"When we examined the brains of these animals, not only did we discover that we could partially protect their dopaminergic neurons from the toxic effects of alpha synuclein accumulation, but we also had evidence that these animals had aggregates. smaller and less numerous than animals, who received an injection of saline instead of GM1 ", explains Dr. Schneider.

In addition to protecting brain cells from death, treatment has also reversed some early motor symptoms, the team said on June 10 in the newspaper. Scientific reports.

The researchers suspect that less GM1 in the brain of patients with Parkinson's disease could facilitate 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 slow down this pathological process and slow down the progression of the disease, which we had already seen in a clinical trial on GM1 in Parkinson's disease patients, "says Dr. Schneider.

The team is currently monitoring their findings to determine what other GM1 effects might have on alpha-synuclein.

"It's important to understand how GM1 works because there may be other ways to manipulate GM1 levels in the brain to have a beneficial effect," Dr. Schneider said.