Submicron-level structural alterations of amyloid proteins often occur prior to the onset of neurodegenerative diseases and before gross changes in the brain tissue can be detected with classical methods. Much is unknown about what causes diseases such as Alzheimer’s and Parkinson’s since the initial pathological events have not been able to be observed in the living brain tisuue. That is why developing preventive treatments is challenging. But new techniques and instruments available at MAXIV at Lund University shed light on these molecular mysteries.
“With OPTIR, we can follow the formation of structures that precede the aggregation of amyloid proteins directly in the living tissue.
Optical photothermal infrared microspectroscopy (O-PTIR) enables time-resolved submicron investigation of chemical and structural changes of diverse biomolecules in their native conditions inside the living tissue. This technique has been used by MultiPark researchers in a new study led by Oxana Klementieva. Together with Daniella Rylander Ottosson from MultiPark and Darcy Wagner and Nicholas Leigh from the Stem Cell Center, they have developed an approach that allows structural studies in living samples. One example of what can be observed in living brain tissue is the formation of beta-sheet structures, characteristic of amyloid proteins involved in Alzheimer’s and Parkinson’s.
“With OPTIR, we can follow the formation of structures that precede the aggregation of amyloid proteins directly in the living tissue. That was not possible before due to the fact that living tissues are mainly comprised of water and this interferes with infrared-based microspectroscopy approaches.”, says Oxana Klementieva.
This opens up for investigations of the effect of anti-amyloid drugs in living samples.
Moreover, the researchers can detect associated damage at the submicronscale, something that makes it possible to study potential treatments in acute brain tissue slices, organoids, or cultured neurons. Since it is label-free, proteins can be studied in their native state. This minimizes the risk of interactions between the molecule of interest and drug candidates during the measurements.
“This approach allows us to study molecular structures directly in tissue which has not been possible before. This opens up for investigations of the effect of anti-amyloid drugs in living samples,” concludes Oxana Klementieva.
