Epigenetic Event-Impacting Protein Linked to Alzheimer's Memory Loss
Scientists at the Cleveland Clinic say they have identified a protein in the brain that plays a key role in the memory loss Alzheimer's patients. They reported their study (“Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency”) in Nature Neuroscience.
The protein, Neuroligin-1 (NLGN1), is known to be involved in memory formation but this is the first time it’s been linked to amyloid-associated memory loss, according to the researchers.
In Alzheimer's disease, amyloid beta proteins accumulate in the brains of Alzheimer's patients and induce inflammation. Using animal models, the scientists discovered that during this neuroinflammatory process, the epigenetic modification of NLGN1 disrupts the synaptic network in the brain, which is responsible for developing and maintaining memories. Destroying this network can lead to the type of memory loss seen in Alzheimer's patients.
“We found in rodents that amyloid fibril-induced neuroinflammation enhanced the interaction between histone deacetylase 2 and methyl-CpG-binding protein 2, leading to suppressed histone H3 acetylation and enhanced cytosine methylation in the Nlgn1 promoter region and decreased NLGN1 expression, underlying amyloid-induced memory deficiency,” wrote the investigators.
“This discovery could provide us with a new approach for preventing and treating Alzheimer's disease,” said Mohamed Naguib, M.D., the Cleveland Clinic physician who lead the study.
Previous studies from this research group have also identified a novel compound called MDA7, which can potentially stop the neuroinflammatory process that leads to the modification of NLGN1. Treatment with the compound restored cognition, memory, and synaptic plasticity in an animal model.
Significant preliminary work for the first-in-man study has been completed for MDA7 including in vitro studies and preliminary clinical toxicology and pharmacokinetic work, noted Dr. Naguib. The Cleveland Clinic plans to initiate Phase I human studies on the safety of this class of compounds in the near future.