Scientists have uncovered a mechanism through which a toxic brain protein that is a hallmark of Alzheimer’s disease can damage neurons, or brain cells. The team at the Grenoble Institute of Neurosciences in France that made the discovery also suggests a potential way to disarm the mechanism during the early stages of the disease.
The study concerns the functioning of dendritic spines, which are the tiny structures in the branching parts of brain cells that receive signals from other brain cells. It appears that beta-amyloid, a toxic protein that builds up in the brains of people with Alzheimer’s disease, triggers a mechanism that disrupts the functioning of dendritic spines.
Neurons transmit information in the brain and carry signals from the brain to other parts of the body, such as organs and muscles.
When information, in the form of chemical messengers, travels across a synapse from one brain cell to another, branching structures called dendrites bring the signals into the receiving neuron. Dendritic spines are tiny protrusions on the branching structures that actively receive signals from other brain cells.
The recent research reveals how, in brain tissue affected by Alzheimer’s disease, toxic beta-amyloid impairs synapses by reducing the activity of cofilin 1 protein in dendritic spines. Brain cells have a cytoskeleton that not only upholds their three-dimensional structure but is also responsible for the dynamic transport of substances inside the cell.
Cytoskeletons have this ability because they consist of highly active actin filaments, which, as Martínez explains, “are anchored but are constantly moving as if they were an escalator.” Cofilin 1 breaks the filaments into separate actin units, “a task that keeps the dynamics active,” he adds.
Phosphorylation, or the addition of a phosphoryl group, to cofilin 1, however, renders the protein inactive. The researchers observed how exposure to beta-amyloid peptides in cultured brain cells led to more phosphorylated cofilin 1. This reduced the dynamism of actin filaments and, in turn, impaired the ability of dendritic spines to receive signals.
Martínez says that the study findings support the notion that targeting ROCK and cofilin 1 during the early stages of Alzheimer’s disease might potentially avert the damage that beta-amyloid inflicts on dendritic spines and synapses.
He suggests that further research into drugs that “specifically stop that phosphorylation” of cofilin 1 in brain cells could be a promising avenue for finding new Alzheimer’s disease treatments.