Dr. David Horrobin has suggested that cell membrane breakdown may play a role in the progression of HD. The over expression of the enzyme called PLA2 is thought to be the cause of cell membrane breakdown. It turns out that a component of fish oil known as eicosapentaenoic acid (EPA) inhibits PLA2. That is why EPA was tested as a treatment for HD.
In my opinion Dr. Horribin is a remarkable researcher equal in insight to Dr. Prusiner. It now appears that Dr. Horrobin is correct. In my opinion he has given us an effective treatment for HD. This is speculation and Dr. Horrobin loves speculation. A wrong idea is like a cockroach. It disappears with light. A correct idea can lead to wonderful discoveries. At long last there appears to be a treatment for HD.
The following press release suggests why Dr. Horrobin is correct and why EPA compensates for the effects of the mutant HD gene. Huntingtin is thought to a trafficking protein perhaps essential for cell membrane integrity. It is not known how the mutant HD gene signals the over expression of PLA2.
Later I will have more about our hero Dr. David Horrobin--Jerry 10/11/00
Journal of Clinical Investigation 10/11/00
Cells rely on the Golgi apparatus to sort secreted proteins bound for different intracellular destinations. Membrane vesicles derived from this organelle may be targeted to the lysosome [a sac like cellular organelle that contains various hydrolytic enzymes] or the apical[narrow part] or basolateral surfaces of a polarized cell, or they may be held in the cytoplasm awaiting a specific signal for exocytosis [the release of cellular substances (as secretory products) contained in cell vesicles by fusion of the vesicular membrane with the plasma membrane and subsequent release of the contents to the exterior of the cell]. Here, Choukroun and colleagues show that Golgi structure and function depend on local lipid metabolism. Phospholipase A2 (PLA2) cleaves phospholipids to generate arachidonic acid, the precursor of many bioactive lipids, as well as lysophospholipids, which are thought to regulate membrane fusion during protein secretion.
Choukroun et al. report that PLA2 associates with the cell’s Golgi fraction, and they show that overexpression of the enzyme disrupts the organization of the Golgi apparatus and specifically blocks the trafficking of certain constitutively secreted proteins, while allowing other cargo proteins to be packaged normally into regulated secretory vesicles.
The fragmentation of the Golgi apparatus seen in PLA2-overexpressing cells is similar to a change that occurs during mitosis [cell division]. The authors indicate that PLA2 activity rises during this period of the cell cycle, and they suggest that the accumulation of phospholipid metabolites in the Golgi membrane causes this organelle to vesiculate [ become blister like] during cell division.