Alzheimer’s research moves forward

Recent research at Ohio State University in America has made progress in identifying a single enzyme which may help in treating Alzheimer’s

Alzheimer’s disease is an awful affliction, with sufferers remaining physically healthy whilst losing their mental capabilities. This reduction in brain function is associated with a build up of plaques in the brain; these being formed from small proteins known as amyloid-beta peptides (Aβ peptides).

Recent research undertaken at Ohio State University, by a team led by Sung Ok Yoon, on a particularly aggressive form of the disease, found that deleting a single enzyme in the studied mice decreased the concentration of plaques by 90 per cent. This decrease was associated with the retention of 80 per cent of normal brain function in year old mice and of 86 per cent of the neurons found in wild type mice.

The enzyme responsible for these detrimental plaques is JNK3, which stimulates a protein that produces Aβ peptides.

JNK3 is activated in a pathway that begins with Aβ peptides activating the enzyme AMP Kinase; this causes a cascade of reactions that eventually result in the silencing of the mTOR pathway, which is responsible for protein synthesis in a variety of cell types.

The silencing of the mTOR pathway then causes the protein synthesis machine of the cell, the endoplasmic reticulum (ER), to enter a stress response and it is as a part of this stress response that JNK3 is activated. The culmination of all this is the death of the neurons.

High JNK3 concentration results in increased production of Aβ peptides, these then aggregate and form plaques, forming a positive feedback loop which increases in severity with each cycle as more Aβ peptides are produced, forming more plaques and propagating the detrimental cycle.

The missing piece of the puzzle is the trigger for the initial ER stress. However, now that it is known that Alzheimer’s is a metabolic disorder under tight control by JNK3, there are now promising targets for therapy, which will no doubt be the subject of much future research.

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