Alzheimer's disease gene therapy: infect the hippocampus with the SVR gene
Scientists have proposed a way to restore impaired memory
"News of Science"
Alzheimer's disease leads to a whole complex of disorders in the brain. The most famous process is the accumulation of amyloid plaques and tau proteins in the nervous tissue, but the reverse side of the coin is also important - a decrease in the synthesis of many proteins important for brain function. American scientists focused on one of these proteins, CBP, and demonstrated that increasing its synthesis in the brains of sick mice significantly improves their memory.
An important tool for studying Alzheimer's disease is to compare the work of a healthy and affected brain. For example, it is known that CREB proteins play an essential role in ensuring normal memory, and in patients with senile dementia their activity is significantly reduced. These proteins are involved in the transmission of a signal to the cell nucleus and changes in the activity of various genes under the influence of the information received.
Scientists at the Institute for Longevity and Aging Research in San Antonio, USA, using a model of Alzheimer's disease in mice, were able to restore the activity of CREB proteins in the brain of animals by increasing the level of CREB-binding protein CBP (CREB-binding protein). In a study published in the latest issue of the journal PNAS (Antonella Caccamo et al., CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease – VM), the authors constructed a safe virus carrying the SVR gene and injected it into a special structure of the temporal lobe of the brain, hippocampus, mice with genetic disorders characteristic of Alzheimer's disease. At the same time, the level of SVR expression in the hippocampus increased significantly.
The hippocampus is a key brain structure for the formation of many types of memory. In particular, it is necessary when studying in the so-called water maze. In this test, mice must remember the position of an invisible platform in muddy water solely by external spatial landmarks. If the task is not completed, the animals may drown. Mice with genetic disorders did not remember the position of the platform in space and "learned anew" each time. But with increased SVR synthesis in the hippocampus, they did not differ from normal animals. It is important that memory improved despite the fact that the pathological accumulation of beta-amyloid and tau protein remained at the same level.
"One of the ways in which SVR can work is to trigger a domino effect among proteins carrying signals from the synapse to the nucleus of the neuron," says Salvatore Oddo, head of the study. – "And changing the work of the cell nucleus is a necessary component of the formation of long–term memory."
The authors believe that increasing the level of SVR in the adult brain due to the delivery of a viral vector can be an effective therapeutic approach not only for Alzheimer's disease, but also for other disorders of brain functions associated with a decrease in the activity of the CREB protein system. This is reported by Informnauka with reference to EurekAlert (Protein restores learning, memory in Alzheimer's mouse model – VM).
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28.12.2010