News Feature | June 9, 2014

Molecular ‘Scaffold' Could Lead To New Dementia Treatments

By Estel Grace Masangkay

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Researchers at the King’s College London reported the discovery of a molecular ‘scaffold’ which may explain the roots of dementia and motor neuron disease, as well as assist in the development of their potential treatments.

The scientists found that the scaffold allows key cell components to interact. In dementia, the scaffold comes apart and causes problems. “At the molecular level, many processes go wrong in dementia and motor neuron disease, and one of the puzzles we’re faced with is whether there is a common pathway connecting these different processes. Our study suggests that the loosening of this ‘scaffold’ between the mitochondria and ER in the cell may be a key process in neurodegenerative diseases such as dementia or motor neuron disease,” said Professor Chris Miller, lead author of the paper, from the Department of Neuroscience at the Institute of Psychiatry at KCL.

Mitochondria in the cell and endoplasmic reticulum (ER) build close associations and interactions, which enable crucial cell functions. An ER protein called VAPB was observed to bind to a mitochondrial protein called PTPIP51 and form a scaffold. The researchers found that by increasing VAPB and PTPIP51 levels, cell mitochondria and ER formed tighter bonds. Cell functions controlled by the ER-mitochondria scaffold become disrupted in neurodegenerative diseases.

The scientists identified a protein called TDP-43 as a potential culprit in the disruption. TDP-43 is linked to Amyotrophic Lateral Sclerosis (ALS), a form of motor neuron disease, and Fronto-Temporal Dementia (FTD), the second most common form of dementia. Placed among mouse cells in a dish, high levels of the protein caused a loosening of the ER-mitochondria scaffold bonds. This affected certain critical cellular functions linked to ALS and FTD.

Professor Miller said the study findings may lead to the discovery of a new therapeutic target in developing treatments for neurodegenerative diseases. The researchers’ work was published in Nature Communications.

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