Once again about the interaction of tau protein and beta-amyloid in the pathogenesis of Alzheimer's disease
Two abnormal proteins can work in tandem, disrupting the structure and function of mitochondria of neurons
LifeSciencesToday based on the materials of the University of Rochester Medical Center:
Two Defective Proteins Conspire to Impair Nerve Cell's 'Powerhouse' in Alzheimer's Disease
The results of a new study (Quintanilla et al., Truncated tau and Aß cooperatively impair mitochondria in primary neurons), published in the journal Neurobiology of Aging, suggest the possibility that the pathological forms of two proteins, beta-amyloid and tau protein, which are signs of brain pathology in Alzheimer's disease – plaques and neurofibrillary tangles – may act in tandem, damaging mitochondria and reducing the survival of neurons.
These findings are part of the results of the work of several laboratories, which attach particular importance to the development of a number of brain diseases, including Huntington's, Alzheimer's and Parkinson's diseases, to cellular components known as mitochondria.
Mitochondria – tiny energy stations inside neurons and other cells – are constantly on the move, producing large amounts of energy that cells use to live. In addition to energy mitochondria perform other functions, for example, such as maintaining normal calcium levels in the cell. A cell with damaged mitochondria is unable to produce enough energy to maintain its vital activity, cannot maintain the necessary levels of calcium and produces an increased amount of oxidizing molecules that damage it. These kinds of events can occur in the brain in Alzheimer's disease, leading to the inability of neurons to function properly.
"For a number of years, the idea that beta-amyloid and tau protein work together to harm the brain has been spreading more and more among scientists," says Gail Johnson, PhD, professor of anesthesiology, the main author of the article. "The exact relationship between the two pathologies is unclear, but when it comes to their effects on mitochondria in Alzheimer's disease, there may be synergy."
Indeed, recently the interaction of these gamer proteins has attracted more and more attention of researchers: here, for example, is a drawing from an article with the artistic title Amyloid-β and tau – a toxic pas de deux in Alzheimer's disease (Lars M. Ittner & Jürgen Götz, Nature Reviews Neuroscience 12, 65-72, February 2011) – VM.
Professor Johnson's group paid particularly close attention to the pathological form of tau protein, which normally helps to stabilize the transport network of neurons called microtubules. In recent years, scientists such as Professor Johnson have focused on studying the abnormally short form of this protein, known as truncated, or processed, tau, as one of the possible candidates for a role in the development of Alzheimer's disease.
Here is another illustration to the question of processed tau protein and microtubules, at least three years ago – VM.
Professor Johnson's group investigated the mitochondrial performance of rat neurons exposed to beta-amyloid, a common tau protein, a processed tau variant, and a combination of beta-amyloid and two tau variants. In one experiment, scientists tracked the movement of mitochondria through neurons, taking pictures every 10 seconds for a five-minute period.
The most significant changes in mitochondria were observed when beta-amyloid and processed tau were present in the cell together. In this case, the mitochondria had only a third of the electrical potential compared to the control. Mitochondria are usually extremely mobile and distributed throughout the cell. However, in the presence of truncated tau and beta-amyloid, they abnormally stuck together in some parts of the neurons and could not get into synapses, as it happens normally. In general, only about half of the mitochondria retained mobility compared to cells that were not exposed to pathological proteins. Cells exposed to processed tau and beta-amyloid were less able than usual to respond to cellular stress. The amount of reactive oxygen species, or free radicals, in such cells is increased by 60 percent. Mitochondria were fragmented, and their average length was only half of normal organelles.
Changes in neurons probably occur before the patient begins to experience symptoms such as memory loss. Most scientists believe that changes in the brains of patients with Alzheimer's disease begin years or even decades earlier than the signs of the disease become apparent.
"By the time the cells are dead, it's too late to do anything," says Professor Johnson. "Therefore, in the field of Alzheimer's disease research, scientists are looking for early markers and indicators of the disease so that patients can be detected before the onset of massive death of nerve cells. In addition, many laboratories are searching for treatments that target these early events."
Perhaps, Professor Johnson adds, new information about mitochondrial dysfunction in Alzheimer's disease can be used to combat it, as it is probably an important target for therapeutic intervention. Given that Alzheimer's disease is a very complex disease, a monotherapy approach may not be as effective as a combined therapeutic strategy, as is the case in the treatment of other diseases, including cancer and diabetes. To develop effective treatments that can improve the function of mitochondria and neurons, further research is needed on how and why mitochondria are damaged in Alzheimer's disease and other neurodegenerative diseases."
Portal "Eternal youth" http://vechnayamolodost.ru31.05.2011