Alzheimer's disease: new targets
Scientists at the Translational Genomics Research Institute (Phoenix, Arizona), working under the guidance of Dr. Travis Dunckley, have identified three kinase family enzymes that disrupt interactions between brain cells, which may be the cause of memory disorders associated with Alzheimer's disease. The results of the work are published in the January issue of the journal BMC Genomics in the article "High-content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease-related tau hyperphosphorylation".
The experimental results showed that these three enzymes disrupt the functioning of tau protein, a protein that provides the "gluing" of microtubules forming the intracellular framework of neurons and ensuring the functioning of interneuronal synapses. As a result, neurons lose the ability to interact with each other, which has a pronounced negative effect on a person's cognitive ability.
Under normal conditions, kinases regulate the activity of tau protein through the process of tau phosphorylation - the attachment of phosphate groups to the enzyme molecule. This makes it possible to disassemble and reassemble certain fragments of the intracellular framework, if necessary, the destruction of old and the formation of new intercellular contacts. This phenomenon, called "synaptic plasticity" provides the brain's ability to form new memories and preserve them.
However, in some cases, hyperphospholyrization of tau protein leads to the formation of neurofibrillary conglomerates consisting of this protein, the presence of which in the brain is one of the characteristic signs of Alzheimer's disease. The result of this is the destruction of synaptic structures, leading to the loss of cells' ability to interact with each other, and the subsequent death of neurons.
The researchers developed sophisticated tests using short interfering RNAs (siRNAs) that allowed them to analyze the content of 572 known and hypothetical kinase family enzymes in human cells. As a result, they identified 26 enzymes involved in tau protein phosphorylation. Three of them (EIF2AK2, DYRK1A and AKAP13) were responsible for hyperphosphorylation of tau protein and irreversible destruction of synaptic structures formed by microtubules.
Initially, the aim of the work was to search for therapeutic targets for the treatment of Alzheimer's disease, therefore, the next stage of the authors' work will be the search for compounds capable of neutralizing the action of kinases that cause hyperphosphorylation of tau protein.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru According to ScienceDaily: Proteins That Might Contribute to Memory Loss and Alzheimer's Disease Identified.
19.01.2010