amyloid beta가 neuronal cell membrane에 주는 영향

the cause of neuronal death is still unknown. The treatments available are aimed at slowing down the development of dementia and only help to improve quality of life for short periods.

have revealed for the first time the atomic structure of amyloid-beta (Aβ) protein assemblies. The knowledge of this structure reveals a new mechanism of toxicity for these assemblies, with the capacity to disrupt the neuronal membrane, allowing water and ions to pass through it and causing the death of these cells.

Several studies have proposed that the interaction of the Aβ protein with the neuronal membrane is responsible for the neuronal death observed in AD. However, the Aβ protein is a difficult therapeutic target because it is "sticky" and self-assembles, adopting distinct shapes and sizes.

To tackle the instability of the conformations, the team first studied the Aβ protein in vitro—in simplified model systems that mimic the neuronal membrane—to develop conditions to prepare stable Aβ forms of uniform composition and shape. Once the compositions had been identified, they studied their structure and mode of neurotoxicity, establishing a 3-D arrangement of all the atoms making up the Aβ ensemble.

"Our study suggests that some Aβ associations can perforate the membrane of neurons, alter their osmotic equilibrium, and consequently trigger their death,"

 

reference

Sonia Ciudad et al, Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage, Nature Communications (2020). DOI: 10.1038/s41467-020-16566-1