Abstract
Neurodegenerative diseases are caused by the abnormal assembly of toxic proteins, such as amyloid β (A β) in Alzheimer’s disease. Mounting evidence suggests that the morphology of amyloid fibrils is strongly influenced by solution conditions, including protein concentration, ionic strength, pH, temperature, pressure, and gravity. Amyloid formation occurs in a heterogeneous multimolecular crowding environment, typified by the surface of the cell membrane. The aggregation of various amyloidogenic proteins, including A β, can be significantly increased on membranes containing glycolipids, which induce dynamic conformational changes that are crucial for amyloid fibril formation. However, because of varying complexity, the molecular basis of environmental impact on Aβ fibrilization remains to be clarified. Therefore, for deeper understanding of the molecular mechanism behind the amyloid formation, it is necessary to characterize dynamic structural changes and interactions of Aβ molecules in complex microenvironments.
Here, we have reviewed structural studies on Aβ assembly considering environmental factors, highlighting NMR studies of A β in glycolipid clusters.
