"Give with a free hand, but give only your own."
 -- J.R.R. Tolkien The Children of Hurin
- D-Ribose -

General Information:

Wikipedia entry:
Dr. Ray Shahelien entry: 



D-Ribosylated Tau forms globular aggregates with high cytotoxicity.
Chen L, Wei Y, Wang X, He R.
State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, 100101 Beijing, China.
Cell Mol Life Sci. 2009 Aug;66(15):2559-71. Epub 2009 Jun 11.

Although the glycation of Tau that is involved in paired helical filament formation in Alzheimer's disease has been widely studied, little attention has been paid to the role of D-ribose in the glycation of Tau. Here, we show that Tau is rapidly glycated in the presence of D-ribose, resulting in oligomerization and polymerization. Glycated derivatives appeared after 24 h incubation. Western blotting indicated the formation of advanced glycation end-products (AGEs) during initial stages of glycation. Thioflavin T-positive (ThT-positive) aggregations that appeared from day 4 indicated the globular-like features. Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globular-like. Kinetic studies suggested that D-ribosylated Tau is slowly oligomerized and rapidly polymerized with ThT-positive features. Moreover, D-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis. This work has demonstrated that D-ribose reacted with Tau protein rapidly, producing ThT-positive aggregations which had high cytotoxicity.
PMID: 19517062

I was able to get the full text of the article from my school's library (it helps that the university has a medical school). No, I don't understand most of it. But I keep trying to educate myself on the terms I don't understand. Wikipedia is a great help. Even if it sometimes has errors, it provides a good starting point.

An important term in this discussion is "glycation": "(sometimes called non-enzymatic glycosylation) is the result of a sugar molecule, such as fructose or glucose, bonding to a protein or lipid molecule without the controlling action of an enzyme. All blood sugars are reducing molecules. Glycation may occur either inside the body (endogenous glycation) or outside the body (exogenous glycation). Enzyme-controlled addition of sugars to protein or lipid molecules is termed glycosylation; glycation is a haphazard process that impairs the functioning of biomolecules, whereas glycosylation occurs at defined sites on the target molecule and is required in order for the molecule to function. Much of the early laboratory research work on fructose glycations used inaccurate assay techniques that led to drastic underestimation of the importance of fructose in glycation."

The paper says that D-ribose is produced both internal to cells and externally, so cells are continuously exposed to this simple sugar. It may be that while D-ribose is an important chemical in intracellular processes, dietary D-ribose may have no effect since apparently the body produces the stuff anyway.

The type of tau protein corruption described in the paper caused by "ribosylation" is "clumping". In AD, tau aggregations are always described as twisted helical pairs, not clumps. However, other neurodegenerative diseases such as the FTD corticobasal degeneration (CBD) DO have this characteristic. What I still want to find out is, are the clumped tau proteins of CBD the same as those described in the D-ribose paper? If so, perhaps the problem is that D-ribose *is* being produced, but not used. It just hangs around. Eventually, it runs into a tau protein, binds with it in some random fashion, and clumps form.

Some confusing thoughts and questions come to mind. I'm just thinking in writing here...

Say for this case there are mitochondria in a neuron that are still functioning and converting glucose to D-ribose, which if I understand the process correctly, is used to create ATP (adenosine triphosphate). I understand that ATP is used and recycled over and over again as the currency of energy for cellular processes, but does it need to be replaced every so often? Do ketones allow malfunctioning cells to use the D-ribose instead of letting it just float around until it causes mischief? But then, if you can live on medium chain triglycerides as a back-up energy source, and D-ribose is needed to create ATP, do cells eventually need glucose to replace lost ATP?

For the case of CBD (corticobasal degeneration) or PSP (progressive supranuclear palsy), perhaps D-ribose is not a good thing to add to the diet, or at best it has no effect; whereas for congestive heart failure it is. For CBD and PSP, there may be an excess of D-ribose. But maybe the other supplements mentioned in the "Sinatra solution" of magnesium, L-carnitine (acetyl-L carnitine for the brain?), and CoQ10, along with MCTs, would help use up the excess D-ribose before it caused problems.

Some other aticles:

1. Chen L, Wei Y, Wang X, He R. D-Ribosylated Tau forms globular aggregates with high cytotoxicity Cell Mol Life Sci. 2009, 66(15), 2559-2571.

2. Lan Chen, Yan Wei, Xueqing Wang, Rongqiao He (2010) Ribosylation rapidly induces a-synuclein protein into advanced glycation end products in molten globules with high cytotoxicity. PLoS ONE 5(2): e9052.

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Updated: July 2, 2012
Inception: July 2, 2012