It may not actually be too difficult to find other molecules that do this, it’s just that it hasn't been clear what to look for until recently. A good tactic now is to search for other molecules that have this same highly targeted effect and to see if these can be used as the starting point for developing a future therapy.
- Sam Cohen
A molecule that can block the progress of Alzheimer’s disease at a crucial stage in its development has been identified by researchers in a new study, raising the prospect that more such molecules may now be found.
The report shows that a molecular chaperone, a type of molecule that occurs naturally in humans, can play the role of an “inhibitor” part-way through the molecular process that is thought to cause Alzheimer’s, breaking the cycle of events that scientists believe leads to the disease.
Specifically, the molecule, called Brichos, sticks to threads made up of malfunctioning proteins, called amyloid fibrils, which are the hallmark of the disease. By doing so, it stops these threads from coming into contact with other proteins, thereby helping to avoid the formation of highly toxic clusters that enable the condition to proliferate in the brain.
This step – where fibrils made up of malfunctioning proteins assist in the formation of toxic clusters – is considered to be one of the most critical stages in the development of Alzheimer’s in sufferers. By finding a molecule that prevents it from occurring, scientists have moved closer to identifying a substance that could eventually be used to treat the disease. The discovery was made possible by an overall strategy that could now be applied to find other molecules with similar capabilities, extending the range of options for future drug development.
The research was carried out by an international team comprising academics from the Department of Chemistry at the University of Cambridge, the Karolinska Institute in Stockholm, Lund University, the Swedish University of Agricultural Sciences, and Tallinn University. Their findings are reported in the journal Nature Structural & Molecular Biology.
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Image: Transmission electron microscopy image showing a molecular chaperone (the black dots) binding to thread-like amyloid-beta (Aβ42)
Credit: S. Cohen
Reproduced courtesy of the University of Cambridge
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