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Nanoscale imaging provides clues towards dementia treatment

Neurodegenerative diseases such as Alzheimer’s or Parkinson’s are associated with the uncontrolled aggregation of proteins into structures called amyloid plaques. One of the difficulties with studying amyloid is its exceptional structural heterogeneity at a small scale. As a result, classical techniques are not able to capture the complexity of the different amyloid structures, essential to our understanding of the disease and to design efficient treatments. Researchers at IMDEA Nanociencia have now combined two advanced imaging methods to shed light on how a specific amyloid-targeting molecule works.

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This molecule, developed by collaborators at the University of Tokyo, is able to selectively bind to amyloid aggregates and is only activated by light irradiation, avoiding secondary effects. The activated molecules produce reactive oxygen species that break up the aggregates into non-toxic fragments. The use of light to activate the molecules provides great spatiotemporal control of the therapeutic action

This collaboration has enabled the nanoscale visualization of the amyloid degradation mechanism induced by the photoactive molecule, demonstrating how the activity depends on the amyloid structure and composition. The study, which has been published in the Journal of the American Chemical Society, highlights that amyloid structural heterogeneity should be taken into account when designing new strategies to treat amyloid-related diseases.

These results are an outcome of the AMYLIGHT project, led by Dr. Cristina Flors at IMDEA Nanociencia in Madrid and Dr. Youhei Sohma at the University of Tokyo. The project is funded by the Spanish Agencia Estatal de Investigación and the Japan Agency for Medical Research and Development to celebrate 150 years of diplomatic relations between the two countries.

P. Bondia, J. Torra, C. M. Tone, T. Sawazaki, A. del Valle, B. Sot, S. Nonell, M. Kanai, Y. Sohma, C. Flors. Nanoscale view of amyloid photodynamic damage, J. Am. Chem. Soc. 2020, 142, 922-930.