The role of biomembrane in amyloid toxicity and small molecules protecting the membrane from amyloid-induced damage

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by dementia and memory loss for which no cure or prevention is currently available. Amyloid toxicity is a result of non-specific interaction of toxic amyloid oligomers with the neuronal cellular membrane.

We used atomic force microscopy (AFM), atomic force spectroscopy (AFS), black lipid membrane (BLM) electrophysiology and surface plasmon resonance (SPR) to study amyloid aggregation and interaction of amyloid beta (1-42) peptide with model lipid membranes, which mimic neuronal cellular membrane in health and in AD. We demonstrated that healthy membrane models are less susceptible to amyloid damage then membrane models mimicking AD-neurons. This ability of amyloid to recognize the changes in membrane structure and properties opens possibilities to protect the membrane against amyloid toxicity. We studied effects of small membrane-active molecules that can change the properties of lipid membranes and protect the membrane from amyloid-induced damage. We found that melatonin partitions into the membrane and reduces amyloid-membrane binding and membrane damage by amyloid. Interestingly, melatonin efficiently protects the membrane models mimicking early stages of AD but not the late stage of AD. The role of membrane properties and lipid composition in these protective mechanisms are discussed, as well as the membrane protection by other molecules such as trehalose sugar and Li salts. These findings contribute to a better understanding of the molecular mechanisms of AD and aid to the development of novel strategies for its cure and prevention.