Structural Biology of Neurodegenerative Diseases: Drug Design and Therapy

FERNANDEZ, CO

Buenos Aires

Conferencia; Frontiers in Bioscience; 2012

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. The aggregation of the protein alpha-synuclein (AS) and Ab peptide are recognized as critical steps in the etiology of Parkinson and Alzheimer diseases, respectively. The study of the structural and toxic mechanisms related to amyloid formation is critical to advance in the design of a therapeutic strategy. The identification of aggregation inhibitors and the investigation of their mechanism of action are fundamental in the quest to mitigate the pathological consequences of amyloid formation. By the combined application of a battery of NMR techniques we have addressed structural and molecular unresolved details related to the mechanistic basis behind the inhibitory effects of anti-amyloud compounds.