Chapter 4: Structural Insights Into the Amyloidogenic Aβ and Tau Species in Alzheimer's disease Pathophysiology: Defining Functional Motifs for Therapeutic Interventions Check Access

The misfolding and subsequent amyloidogenic aggregation of the Amyloid β (Aβ) peptide and Tau protein has been recognized as the major hallmark in Alzheimer's disease pathophysiology. Therefore, understanding the molecular architecture of amyloid fibrils under various conditions is essential for developing therapeutic interventions. Over the decades, several parallel studies around the globe have been focusing on defining novel therapeutic target motifs. However, the highly dynamic attributes of the functional intermediates have stymied much of the progress in gaining crucial structural information. Nevertheless, high-resolution solid- and solution-state NMR spectroscopy have served as an indispensable means to gain essential insight into the structure-function correlation prompting innumerable studies to define newer therapeutic strategies. In this chapter, we have mainly focused on the structural characteristics of Aβ and Tau aggregates as obtained mostly from the NMR perspective. Further, careful experimental planning could guide us to uncover the complex stages of amyloid aggregation, focusing on transient intermediates. This would, in turn, reveal efficient target motifs for effective therapeutic interventions.