A possible role for π-stacking in the self-assembly of amyloid fibrils

Ehud Gazit*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Amyloid fibril formation is assumed to be the molecular basis for a variety of diseases of unrelated origin. Despite its fundamental clinical importance, the mechanism of amyloid formation is not fully understood. When we analyzed a variety of short functional fragments from unrelated amyloid-forming proteins, a remarkable occurrence of aromatic residues was observed. The finding of aromatic residues in diverse fragments raises the possibility that π-π interactions may play a significant role in the molecular recognition and self-assembly processes that lead to amyloid formation. This is in line with the well-known central role of π-stacking interactions in self-assembly processes in the fields of chemistry and biochemistry. We speculate that the stacking interactions may provide energetic contribution as well as order and directionality in the self-assembly of amyloid structures. Experimental data regarding amyloid formation and inhibition by short peptide analogs also support our hypothesis. The π-stacking hypothesis suggests a new approach to understanding the self-assembly mechanism that governs amyloid formation and indicates possible ways to control this process. - Gazit, E. A possible role for π-stacking in the self-assembly of amyloid fibrils.

Original languageEnglish
Pages (from-to)77-83
Number of pages7
JournalFASEB Journal
Issue number1
StatePublished - 2002


  • Alzheimer's disease
  • Amyloid-related proteins
  • Aromatic residue


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