Lipid Deficiency Linked to Parkinson’s

Drs. Guy and Kim Caldwell

Dr. Kim Caldwell and Dr. Guy Caldwell co-authored a paper that was published in Proceedings of the National Academy of Sciences.

From the October 2014 edition of Desktop News | A study co-authored by researchers in The University of Alabama’s Caldwell Lab focuses on the potential roles lipids have in the death or malfunction of dopamine-producing neurons, which leads to symptoms associated with Parkinson’s disease.

The study was recently published in the Proceedings of the National Academy of Sciences and was led by senior researcher Dr. Stephan Witt at Louisiana State University Health Sciences Center. The University of Alabama’s lead author on the study was Siyun “Alice” Zhang, a third-year doctoral student at UA, and was co-authored by Dr. Guy Caldwell, UA professor of biological sciences, and Dr. Kim Caldwell, UA professor of biological sciences. This is the third article published in the Proceedings of the National Academy of Sciences by the Caldwell lab since March.

The study focused on phosphatidylethanolamine, a lipid known as PE. The article details how low levels of PE lead to high-levels of alpha-synuclein, a protein previously linked to Parkinson’s. It also shows the promise a second lipid, ethanolamine, or ETA, has in boosting PE levels.

“This gets right to the heart of understanding, possibly, the mechanism by which one form of lipid is impacting the process of neuron degeneration,” Guy Caldwell said.

To function correctly, proteins must fold properly within cells. One misfolding, as can occur when extra copies of the protein alpha-synuclein are present, can lead to others and, subsequently, to aggregation, or clumping, of proteins. Aggregation of proteins can lead to neuron malfunction or cell death.

Previous research had shown that excess alpha-synuclein can serve as an intra-cellular “roadblock,” preventing proteins, dopamine and other necessities from being delivered to their proper locations in cells. This delivery disruption can lead to serious disorders.

“That situation is being applied here, but in a different way,” Caldwell said. “We’re gaining a better understanding of the importance these lipids, which are components of cellular membranes, have in maintaining proper trafficking.”

A proper link with alpha-synuclein helps “lipid rafts” in their transport of proteins.

“As the name implies, lipid rafts are like rafts of fat,” Caldwell said. “If alpha-synuclein can’t associate with those rafts, it could be a toxic situation for these cells.”

Using yeast and the time nematode C. elegans as the laboratory models, the researchers showed they could reverse the delivery problem by adding ETA to the mix.

“This supplementation of ETA basically tells us that if we can restore the amount of PE that is being made, we can create a healthier situation in neurons, and this might help them survive longer,” he said.

Additional study is needed in rodents and patient-derived stem cells before knowing how beneficial the discovery could eventually prove, Caldwell said.

Perhaps one day, Caldwell said, a supplement could be developed to prevent the decline of PE or possibly a drug could be developed to activate an enzyme that converts ETA to PE.

The research was supported, in part, by grants from the National Institutes of Neurological Disorders and Stroke.