Physical chemistry renews hope in quest to cure Alzheimer

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The course of the disease is irreversible, and ultimately patients need care and often become socially isolated.

Munich: An increasing number of people, particularly the elderly, are developing Alzheimer’s disease.

Alzheimer’s disease is triggered by the death of millions of neurons in the brain. In affected brain tissues, clumps of the protein called Tau have a major contribution to malfunction of neurons and eventually to their death.

The course of the disease is irreversible, and ultimately patients need care and often become socially isolated. The Tau protein itself is not harmful and has a vital function in living cells as it binds to Microtubule, the main component of the cell structure.

Only when a person develops Alzheimer’s, Tau occurs in an altered state in neurons and clump together to form toxic species. But what triggers this devastating change and how is chemistry able to modify them?

The scientific discovery was reported by Dr. Elias Akoury, a Lebanese researcher and academic at the Ludwig-Maximilian University of Munich (LMU, Germany) who led an international team of scientists comprising researchers at Utrecht University (The Netherlands), the German Center for Neurodegenerative Diseases, the Max Planck Institute for Biophysical Chemistry (Göttingen, Germany), and the University of South Florida (USA).

By applying Physical Chemistry and the state-of-the-art high-resolving techniques Nuclear Magnetic Resonance (NMR) Spectroscopy and X-Ray Diffraction (XRD), the researchers determined the structure of the protein at atomic resolution and highlighted the inhibition of protein aggregation.

THE DISCOVERY

There is currently no cure for Alzheimer’s disease, but some chemical agents have been observed to inhibit the formation of protein though little is known about the mechanism.

The hope is that such agents may someday prevent or even cure diseases caused by protein aggregation.

The scientists have unraveled the interactions between Tau protein and two of such agent molecules: Phthalocyanine Tetrasulfonate (PcTS) and Methylene Blue (MB).

The researchers discovered that PcTS binds to specific parts found on Tau and prevent the aggregation to filaments by prompting the formation of smaller non-toxic species, called oligomers.

The oligomers are structurally distinct from those associated with Alzheimer’s disease.

Remarkably, the active ingredient of MB is multivalent. The substance is synthetic, was first made in 1876, and has since served not only as a blue dye but also for medical purposes, such as the treatment of Malaria and prevention of urinary tract infections.

Meanwhile, it is also being discussed as a remedy for Alzheimer’s. “The mode of action of Methylene Blue was previously unclear and we have elucidated the mechanism by which it inactivates the function of certain building blocks in the protein” emphasizes Dr. Akoury.

The researchers also found evidence that the drug keeps the proteins like a spacer at a distance. These findings could be incorporated into the production of modified forms and the development of therapies.

There is no effective treatment for this disease to date but with the use of physical and computational chemistry, these discoveries provide a new approach for investigating the emergence of Alzheimer’s disease.

 

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