January 29, 2013

Methylation and Tangles:

Tangled Tracks in the Brain:

In an earlier Blog we described a key feature of Alzheimer's Disease - neurofibrillary tangles in the brain.  Tangles are formed from a protein called tau.

Tau mainly occurs in long fibre-like extensions of nerve cells called axons.  Tau binds to structures called microtubules.  It helps regulate their length. It also controls their ability to transport key nutrients and messengers within the cell. You can perhaps think of microtubules as railway tracks carrying goods within the cell, and tau as the supporting sleepers. 

Regulating tau:

Tau is regulated by a process called phosphorylation.  But this can go wrong.  For example, tau is phosphorylated too much in Alzheimer's Disease. This causes tau to clump together and form tangles.

Phosphorylation:

The amount of tau phosphorylation represents a fine balance between the competing effects of two enzyme groups - kinases and phosphatases.  Kinases add phosphate groups to tau; phosphatases remove them.

The most active tau phosphatase is called PP2A.

Methylation:

Methylation is a key step in PP2A activation. And as we have already seen, impaired methylation occurs with high homocysteine levels.

So, high homocysteine and impaired methylation reduce PP2A activity.  As a result, phosphate groups aren't removed from tau.  It becomes 'sticky', and forms tangles.  Several studies have clearly shown this link between homocysteine and tangle formation.


In our Next Update we will look at how high homocysteine is linked with the formation of the other key feature of Alzheimer's Disease - amyloid plaques.








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