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- D-Ribose -
General Information:
Names:
Wikipedia entry:
Dr. Ray Shahelien entry:
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Observations:
D-Ribose
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
http://www.ncbi.nlm.nih.gov/pubmed/19517062?ordinalpos=1&itool=PPMCLayout.PPMCAppController.PPMCArticlePage.PPMCPubmedRA&linkpos=1
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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References:
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Updated: July 2, 2012
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