These diseases are caused by proteins that self-aggregate in the brain: Aβ for
Alzheimer's, α-syn for Parkinson's. But there are several modes of aggregation: oligomers, fibers, and amyloid plaques. Among these structures, the oligomers are the most neurotoxic forms and those which appear at the most early steps of pathogenesis.
These oligomers create pores in the membrane of brain cells. These structures are called "amyloid pores". Calcium Ca2+ ions2+ enter the cells through these pores, triggering a neurotoxic cascade: oxidative stress, hyperphosphorylation of the tau protein, synaptic dysfunction. These events cause major functional disturbances in the affected brain cells and ultimately their degeneration and disappearance: pretty soon the disease develops.
The formation of amyloid pores is the earliest stage in Alzheimer's disease and Parkinson's disease.
In both diseases, this step involves the attachment of amyloid proteins to the surface of neurons and astrocytes, at the level of particular membrane structures called gangliosides.
Our researchers have elucidated the biological code controlling the recognition of gangliosides by amyloid proteins. They were thus able to model, on an atomic scale, the entire process of amyloid pore formation. In the center of the pore, the gray disc is a Ca2+ ion2+ entering the cell.
These in silico simulations made it possible to create the AmyP53 solution.