Surgery News

Fish oil protects against neurodegenerative diseases

January 15, 2016

He will present these findings for the first time on Sunday, April 19, 2009 at 10:30 a.m. at the Ernest N. Morial Convention Center, Nouvelle C Room, at the American Society for Nutrition, Experimental Biology 2009 Annual Meeting.

With funding from the National Eye Institute of the National Institutes of Health, Dr. Bazan and his colleagues developed a cell model with a mutation of the Ataxin-1 gene. The defective Ataxin-1 gene induces the misfolding of the protein produced by the gene. These misshapened proteins cannot be properly processed by the cell machinery, resulting in tangled clumps of toxic protein that eventually kill the cell. Spinocerebellar Ataxia, a disabling disorder that affects speech, eye movement, and hand coordination at early ages of life, is one disorder resulting from the Ataxin-1 misfolding defect. The research team led by Dr. Bazan found that the omega three fatty acid, docosahexaenoic acid (DHA), protects cells from this defect.

Dr. Bazan's laboratory discovered earlier that neuroprotectin D1 (NPD1), a naturally-occurring molecule in the human brain that is derived from DHA also promotes brain cell survival. In this system NPD1 is capable of rescue the dying cells with the pathological type of Ataxin-1, keeping their integrity intact.

"These experiments provide proof of principle that neuroprotectin D1 can be applied therapeutically to combat various neurodegenerative diseases," says Dr. Bazan. "Furthermore, this study provides the basis of new therapeutic approaches to manipulate retinal pigment epithelial cells to be used as a source of NPD1 to treat patients with disorders characterized by this mutation like Parkinson's, Retinitis Pigmentosa and some forms of Alzheimer's Disease."

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It was now time for stage two, and therefore the turn of Dr. Craig Lindsley, head of Medicinal Chemistry and Director of the Vanderbilt Specialized Chemistry Center for Accelerated Probe Development. His task was to create an effective probe compound.

"There is no point optimizing a molecule's potency in vitro if it turns out not to work in vivo," says Lindsley. His probe works in both. The team now is trying the compound in mouse and rat models of Alzheimer's and schizophrenia to determine what dose range restores the appropriate level of signaling through the targeted receptor. In addition, this compound provides a tool of unprecedented selectivity that will allow the researchers to tease apart the basic role of the M1 and M4 receptors in CNS function and disease states to degree that has never before been possible.

The team hopes that within a year they will have a compound ready to license to a pharmacological company that can continue with preclinical development and then onward to human trials.

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