The role of polyunsaturated fatty acids in neurodegeneration

Excitotoxicity, oxidative stress and inflammation are core processes that play leading roles in neurodegenerative diseases. Polyunsaturated fatty acids (PUFAs) methodically contribute to and impair the cells' defensive mechanisms against these destructive processes, leading to cellular over-excitation and death. Examples of PUFAs include corn oil, safflower oil, soybean oil and some margarines.
Fish oils and membrane pumps

Cells with respiratory damage produce less energy. When energy in a cell falls, membrane pumps --which protect against calcium overload -- falter and the cell is no longer able to keep intracellular calcium concentrations under control. Loading of the mitochondria with calcium beyond a certain point disrupts its function, further decreasing energy availability. Fish oil (DHA and EPA) inhibits these membrane pumps, which normally protect the cell from over-excitation.

Mitochondria, oxidative stress and PUFAs

The mitochondrion is the site where energy production occurs and aging is associated with mitochondrial dysfunction and increased oxidative stress. PUFAs, especially the longer chain varieties (DHA and AA), accumulate preferentially in the mitochondria with aging, displacing the more stable, saturated varieties that predominate during youth. PUFAs, like a toxin, disrupt mitochondrial function, while saturated fats support it by decreasing inflammation and oxidative stress.

The role of cellular energy production

The brain has high requirements for energy, creating it almost entirely by mitochondrial oxidative phosphorylation. Therefore, mitochondrial integrity is integral for high rates of energy production and neuronal survival. Vitamin E is an antioxidant that normally keeps PUFAs in check; however, fish oil induces vitamin E deficiency. Saturated fats decrease the requirements for vitamin E and keeps energy production high, helping to prevent neuronal degeneration.

PUFAs (along with lactic acid, low oxygen, estrogen and endotoxins) increase tumor necrosis factor (TNF), which causes the cell to take in too much calcium and impairs respiration (through CO). Aspirin inhibits TNF formation and lowers free radical production; along the same line, magnesium can protect against calcium overload.

Final words

It has been argued that linoleic acid and alpha-linolenic acid are absolutely essential, and that they are somehow safer and more beneficial than the longer and more unsaturated acids. However, lipid peroxidation processes concern all PUFAs, and the main PUFA in mammalian tissue is linoleic acid.

It is clear that PUFAs impair the cell's ability to overcome stressful events. PUFAs diminish energy production, which paradoxically excite cells to death, culminating in the manifestation of the neurodegenerative diseases. Keeping the cell operating efficiently and avoiding the substances that impair cellular functioning may help to prevent the onset or delay the progression of these disorders.

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