Studying structure and aggregation of amyloid proteins using small organic compounds as molecular probes

ARIEL ALEJANDRO VALIENTE GABIOUD; CARLOS BERTONCINI; TIAGO OUTEIRO; CHRISTIAN GRIESINGER; CLAUDIO O. FERNANDEZ

Villa Carlos Paz

Congreso; XLII Reunión anual de la Sociedad Argentina de Biofísica; 2013

The misfolding of proteins into a toxic conformation is proposed to be at the molecular foundation of a number of neurodegenerative disorders including Alzheimer and Parkinson?s disease. One common and defining feature of protein misfolding diseases is the formation and deposition of amyloid-like fibrils. Currently, no preventive therapy is available for Parkinson and Alzheimer diseases. Identification of therapeutic drugs is not only complicated by a lack of understanding of many of the key aspects of the pathogenesis of these diseases but also by the multifactorial etiology of them. The aggregation pathway of the proteins linked to these disorders represents then an obvious target for therapeutic intervention. The detailed understanding of the phenomenon of amyloid fibrillation and its inhibition is therefore highly clinically important. Our work paves the road for the high resolution characterization of the modulatory effect of small compounds on amyloidogenic intrinsically disordered proteins, which is critical for the rational design of efficient anti-amyloid agents to treat Parkinson and Alzheimer?s disease.