2023-12-18 21:15:25
The aggregation of Tau protein in the brain is a marker of several neurodegenerative diseases including Alzheimer’s disease. Recent studies show that the formation of these Tau aggregates, also called amyloid fibers, coincides with the presence of other biomolecules, the nature and organization of which are not yet elucidated. Identify alive which molecules induce the aggregation of the Tau protein and form deleterious neurofibrillary tangles would be a major advance for the understanding of Alzheimer’s disease and other pathologies associated with the Tau protein (tauopathies).
In vitro, numerous studies have established that negatively charged molecules, such as sugars, lipids or even nucleic acids (RNA), can induce Tau aggregation. But directly observing to understand which cofactors assemble with Tau to form pathological aggregates is a difficult task because of the nanometer size of amyloid fibers. This technological challenge requires the development of new characterization tools.
Bordeaux teams from Chemistry and biology of membranes and nanoobjects laboratory (CBMN, CNRS/Bordeaux INP/University of Bordeaux) and the Institute of Molecular Sciences (ISM, CNRS/Bordeaux INP/University of Bordeaux) demonstrated that the aggregation of the Tau protein can be induced by the model RNA PolyA, adenine nucleotide chain. To do this, they used a Raman spectroscopy setup. TERS (Tip-Enhanced Raman Spectroscopy) developed at the ISM and which simultaneously allows the visualization and chemical characterization of aggregates a few nanometers in diameter. This Raman spectroscopy technique allowed them to analyze individual amyloid fibers and reveal the insertion of PolyA into the fiber. The integration of the specific vibrational signatures of the Tau protein and adenine makes it possible to simultaneously characterize the protein part and the RNA part of the fiber. This study demonstrated that polyA RNA interacts with several regions of the Tau protein, both those organized in sheets as well as its more disordered regions. Furthermore, strong colocalization is observed between RNA and positively charged residues of the protein. These results, published with the label “ hot topic » in the review Applied Chemistry International Editionallow us to better understand the formation of these aggregates in order to hope to act more upstream on the pathology.
Editor: AVR
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#Alzheimers #elucidating #formation #aggregates #brain