Researchers from the University of Michigan have discovered that a cellular vulnerability could yield a novel target for treating Alzheimer’s disease.
The team found that the thin parts a neuron’s cell membrane are susceptible to a protein called beta-amyloid that collects in the brain of patients diagnosed with this neurodegenerative disorder.
The thinner parts of the neuronal membranes, composed of short fatty acid chains, give access points to amyloid-beta, allowing the protein to puncture and kill those cells, destroying the patient’s ability to make and retain memory.
Essentially, the scientists believe that the formation of lipids with short chains—caused by aging or other physiological means that result in Alzheimer’s—can promote cell death from the accumulation of amyloid-beta.
“We're trying to understand how components of the cell membrane and the physical and chemical properties of the lipid membrane would influence the aggregation of amyloid-beta by a variety of biophysical techniques,” Ayyalusamy Ramamoorthy, the Robert W. Parry Collegiate Professor of Chemistry and Biophysics, said in a statement.
The study was done in what’s called a phospholipid bilayer, which consists of two layers of lipids that are made up of hydrophobic or water-hating and hydrophilic or water-loving phases and look similar to a mixture of oil and water.
A technique called phosphorus-31 nuclear magnetic resonance revealed details at the atomic level within bilayers similar to the way a physician would use an MRI machine to look at tissues in the human body, the researchers examined how the collection of amyloid-beta in thinner membrane fragmented the cellular membrane.
The researchers investigated three types of lipids that varied in thickness. Thicker lipid membranes that composed of longer fatty acid chains attracted and promoted the growth of plaque while the thinner membrane acted sometimes like a lipid and sometimes like a detergent.
The detergent-like fatty acid chains interact with the plaque, allowing that plaque to penetrate the cell membrane.
This lipid bilayer replicates the cell membranes found in neurons.
“Many other labs are investigating the amyloid inhibition by small molecules in solution, but we are doing it in a membrane environment. From our study it is clear that the cell membrane is the hot spot where amyloid-beta becomes crazy,” Ramamoorthy said. “The cell membrane is definitely not like a coffee filter that filters biological events--rather, it is the place where a plethora of biological actions happen.”
Ramamoorthy team is now screening libraries of small molecular compounds that could target the aggregation of amyloid-beta within a person’s cell membrane.
“These findings could be significant in the potential development of compounds to treat the aging-related diseases,” he said.