A team of neuroscientists has discovered a promising method to address cognitive function loss caused by Alzheimer's disease by targeting protein synthesis in an experiment conducted on laboratory mice.
The findings reported by the researchers, published in the journal Science Signaling, reveal that synthetic drugs can rescue the activity of brain cells essential for memory formation from losing their function in individuals affected by Alzheimer's disease. Professor Mauricio Martins-Oliveira, a postdoctoral researcher at the NYU Neuroscience Institute and the lead author of the study, stated: "This study is the first scientific work to show that reversing protein synthesis in the brains of Alzheimer's patients through a pharmacological approach is not only feasible but also highly effective." Currently, treatments for Alzheimer's focus on alleviating symptoms associated with amyloid plaque, neurofibrillary tangles, and neuroinflammation, while this study suggests that adding pharmacological protein synthesis may help revive and protect normal brain activity.
Co-author Sergio Ferreira, a professor at the Federal University of Brazil’s Biophysics Institute, commented: "Synthesis of new proteins in the brain is essential for proper neuronal function, particularly for strengthening memory. We and others have previously shown that impaired protein synthesis in the brain contributes to memory deficits in laboratory mice with Alzheimer's."
Co-author Eric Klan, a professor at the NYU Neuroscience Institute, added: "Given the complex nature of Alzheimer’s disease, identifying and targeting the abnormal molecular pathways that effectively enhance cognition has been challenging in the past. However, our results indicate that stimulating protein synthesis in the brain can restore cognitive functions lost due to Alzheimer's, and we hope this study serves as a step forward in treating this devastating disease."
It is noteworthy that the study primarily focused on the molecule ISRIB, a synthetic molecule capable of enhancing protein synthesis in the brain. ISRIB, developed by scientist Peter Walter from the University of California, San Francisco, targets the initiation of the translation of genetic codes that ultimately stimulates cellular protein synthesis in the brain. The researchers aimed to determine if ISRIB could restore the brain's ability to change for learning and memory retention. Earlier studies showed that the gene translation initiation process was weak in the brains of Alzheimer's patients, leading the team to hypothesize that ISRIB could help re-establish some cognitive functions.
After demonstrating that key components of the protein synthesis mechanism were depleted in the hippocampus—an area of the brain known to play a crucial role in memory—of Alzheimer's patients, the scientists concluded that protein synthesis may also be disrupted. They then tested whether ISRIB could rescue the memory of mice with Alzheimer’s-like conditions through a series of memory tests, such as navigating a maze, and found that ISRIB could indeed restore memory functions in the mice, along with protein synthesis in the hippocampus as well. Additionally, the researchers examined whether ISRIB could restore hippocampal function and cognition in mice with advanced Alzheimer’s-like conditions, and similarly, their results showed that ISRIB could restore synaptic plasticity in the hippocampus, as well as memory functions.
