The study, published in the journal Cell, details how the Orb2 protein, a functional amyloid protein necessary for the consolidation and persistence of long-term memory, progressively alters its three-dimensional structure as the fly ages. Researchers have successfully reconstructed the structural evolution of Orb2 aggregates throughout the adult life of the fruit fly Drosophila melanogaster, a feat not previously achieved with functional amyloids.
The findings suggest that the shape proteins adopt and the ability of their clustered structures to change are closely linked to their function. While Orb2 conformations in young flies promote the synthesis of proteins crucial for memory consolidation, the structures predominant in aging animals lose this capacity, correlating with memory impairment.
One of the most significant conclusions is that this functional decline may not be irreversible. Experiments involving a molecular chaperone called Funes demonstrated that increasing its presence in neurons of aged flies promotes the recovery of Orb2 structural states characteristic of juvenile stages, thereby improving memory.
Javier Oroz, principal investigator of the PLASTIMORF group at IQF-CSIC, notes that this structural plasticity can be crucial for essential physiological processes like memory and for understanding neurodegeneration mechanisms. The research opens new perspectives for understanding the relationship between protein structure, neuronal function, and memory loss, suggesting that regulating the conformational plasticity of amyloids could be a strategy for investigating cognitive decline.
