Main Researcher: Prof. Kobi Rosenblum
Co-researchers: Dr. Elad Stern, Dr. Yifat Segev
Invention area: Neurobiology of Learning and Memory
Inhibition of eIF-2α phosphorylation can be used to improve cognitive functionand/or to treat dementia, including Alzheimer's Disease. In particular, this can be achieved by inhibiting the kinase activity of PKR in a non-toxic manner.
The invention relates to improving cognitive function, and in particular, toimproving learning and/or memory formation. The present invention also relates to treating dementia and in particular to treating Alzheimer's Disease (AD).
AD is one of the most common forms of dementia. It is generally diagnosed in people over the age of 65 years, although early onset is possible. AD is a progressive and terminal disease, for which there is currently no cure.
The ability to form new and stable memories deteriorates with age and is a clear hallmark of different neurodegenerative diseases including AD and frontotemporal dementia. The vast majority of AD cases have complex etiology with multiple genetic and environmental factors influencing pathogenesis. Indeed, different animal models are used to study the complex biology underlying AD
Control of mRNA translation is a major means for regulation of gene expression in responses to external stimuli presented by the changing environment. Translation regulation comprises three major steps: initiation, elongation and termination, where, in eukaryotes, the initiation phase is usually rate-limiting and serves as the target for regulation. Several major signal transduction cascades, including the mTOR and eIF2α pathways, regulate translation initiation in neurons and other cells. Translation regulation in neurons is particularly complex. Major components of the protein synthesis machinery, including ribosome's, translation factors and mRNA are present in dendrites and dendritic spines, and translation can be regulated differentially at the cell body, the synapse and post-synaptic components. Importantly, cellular stress and injury often lead to an increase in phosphorylation of initiation-related proteins such as eIF2α and to subsequent down- regulation of the translation initiation process. The effects of neuronal activity and of distinct neurotransmitter systems on these signaling cascades, and their role in learning and memory and neuronal plasticity are not fully understood.
Applications: A drug for memory enhancement
Read the article :'Israeli researchers find way to improve memory through Alzheimer's-linked molecule':
published in Haaretz Magazine on Nov. 11th 2014. Hebrew Version(PDF) , English version(PDF) , Online version
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