Protein Synthesis Fix may Reverse Cognitive Decline in Alzheimer’s
Restoring protein synthesis in the brain may reverse the cognitive decline associated with Alzheimer’s, according to a study by researchers from New York University (NYU) and the Federal University of Rio de Janeiro (UFRJ).
Current Alzheimer’s treatment research focuses on reducing the phenomena linked to the disease, such as amyloid plaques, neurofibrillary tangles, and neuroinflammation. The study aimed to determine whether restoring protein synthesis would also be beneficial.
“The synthesis of new proteins in the brain is essential for proper neuronal function and, notably, for memory consolidation. We and others have previously shown that impairments in brain protein synthesis contribute memory deficits in Alzheimer’s disease model mice, and that the brains of Alzheimer’s patients exhibit clear signs of impaired protein synthesis. We thus asked ourselves whether rescuing brain protein synthesis might be an approach to improve memory function in Alzheimer’s disease,” said co-senior author Sergio Ferreira, a professor at UFRJ.
“Given the complex nature of Alzheimer’s disease, identifying and targeting abnormal molecular pathways that effectively improve cognition has been challenging,” added co-senior author Eric Klann, a professor at NYU. “Our findings show that jump-starting protein synthesis in the brain can revive lost cognitive functions. We hope that this work can serve as a step forward in treating this devastating disease.”
Previous research found that a cellular quality control mechanism called the integrated stress response (ISR) was found to slow down protein synthesis to weed out problems like cancerous cells, but can get stuck in the ‘on’ position. In 2013, a drug called ISRIB was developed to reverse this (ISRIB stands for ISR InhiBitor).
Previous research with ISRIB had shown positive results in restoring memory function in mice, months after traumatic brain injury (TBI), reversing cognitive impairments in Down Syndrome , preventing noise-related hearing loss, treating certain prostate cancers, and even cognitive enhancement in healthy animals.
The researchers determined that in Alzheimer’s patients, critical components of protein synthesis are depleted in the hippocampus. The researchers hypothesised that some cognitive function could be returned if protein synthesis was restored with ISRIB.
The researchers used mice with Alzheimer’s-like conditions as a model. Testing the mice’s memory (eg with maze runs), they found memory function and hippocampal protein synthesis restored with ISRB. Restoration of hippocampal neural plasticity and memory functions was observed even in simulated advanced Alzheimer’s.
The results indicate that restoring protein synthesis with drugs such as ISRIB, could work together towards reversing cognitive decline from Alzheimer’s in humans.
Source: Medical Xpress
Journal information: “Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer’s disease,” stke.sciencemag.org/lookup/doi … 26/scisignal.abc5429
