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Friday, December 30, 2011

Histones deacetylation - new lead to degenerative diseases?

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This recent article (and that paper) discuss the link between histones abnormality and schizophrenia.

Histones acetylation reduction or "deacetylation" cripples the ability of DNA to encode proteins thus can affects the entire cellullar metabolic and regenerative apparatus, producing effects probably resembling genetic disorders.  (What are histones? Read here)

The study reports particulary strong histone anomaly among schizophrenic patients of young age. This suggests a possible neurodegenerative process indicating a possible mechanism of the pathology of a young brain, that may lead to schizophrenia later in life.

Questions to think about:
  1. Could histone deacetylation anomaly lead to other common degenerative diseases?
  2. How does it affect mitochondria?
  3. Is there a connection between wheat histones (*) (or this) and human histones?
Few more facts about histones and neurological health:

- Since acetylation reduction is done by deacetylation enzymes called "deacetylase", inhibiting of deacetylase should restore the required level of histone acetylation. What are the common deacetylase inhibitors? Quote from the wiki article:

HDIs [Histone Deacetylase Inhibitors] fall into several groupings, in order of decreasing potency[6]:
  • hydroxamic acids (or hydroxamates), such as trichostatin A,
  • cyclic tetrapeptides (such as trapoxin B), and the depsipeptides,
  • benzamides,
  • electrophilic ketones, and 
  • the aliphatic acid compounds such as phenylbutyrate and valproic acid.

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More references:
Scientists discover a brain cell malfunction in schizophrenia
( Note: the link above as well as the original article twit was posted on this blog )

Note (*): interestingly, wheat uses histone disruptors to fight funghi.  New wheat variety introduced in the last century was specifically bread to resist funghi and molds.  Recent wheat variety  = heart diesease and cancer.  Earlier wheat, 19-th century and back = no prob!  Or is it too far out to conclude that?

Latest news (9-Feb-2012):


Scientists make discovery related to atherosclerosis


A research team funded by the National Science Council achieved a breakthrough in molecular--targeted therapy of atherosclerosis by experimenting on the condition’s formation mechanism from the perspective of cardiovascular biodynamics.
The council said discoveries by the team led by National Health Research Institutes [Taiwan] researcher Chiu Jeng-jiann (裘正健) had been recognized by the prominent academic journal Physiological Reviews in a cover story last year.

...the team focused on discovering the mechanism of how different levels of blood flow shear stress could affect molecules related to atherosclerosis formulation. The team was able to demonstrate that oscillated shear stress can increase the performance of several types of histone deacetylase (HDAC) in the endothelium, modulating some transcription factors and gene transcription. A noteworthy discovery is that the third type of HDAC has the important function of modulating oxidation, inflammation and hyperplasia and can be seen as an important targeted therapy for the prevention or treatment of atherosclerosis, Chiu said.

Reference:
"Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives", JENG-JIANN CHIU AND SHU CHIEN, Physiol Rev 91: 327–387, 2011

Update (28/08/2013)


Age-Related Forgetfulness Tied to Diminished Brain Protein (RbAp48)


and


RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein.



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2 comments :

J. Stanton - gnolls.org said...

This is a fascinating lead, Stan.

Whether it pans out or not, I'm quite sure that we haven't yet discovered all the anti-nutrients in food, nor all their potential mechanisms of action. We're still discovering new nutrients after many decades of intense research...and the research on anti-nutrients lags far behind.

JS

Stan Bleszynski said...

It is fascinating indeed and true, we know so little details about the biochemical mechanisms. It is relatively easy (except for members of American medical establishment) to figure out that wheat family of plants are mild health hazards and slow cardiovascular poisons. It is harder to tell exactly why.

I think the same may apply to many if not most plants like beans and cabbage family etc., for different reasons. Those plants seem to be OK for us in the short term but not so good if one eats a lot of that every day. Each plant gives us its own distinct set of problems.
Stan