From asthma and senile dementia
Researchers from the Lewis Katz School of Medicine at Temple University have shown for the first time in animal models that damage caused by tau protein can be repaired.
Initially, the researchers found that the regulation of leukotriene synthesis in Alzheimer's disease and senile dementia is disrupted, especially in the later stages of the disease. In the early stages of dementia, they try to protect nerve cells, but with the progression of the disease, they damage them. The authors tried to block leukotrienes and thus restore memory and learning ability in mice with extensive tau protein lesions.
They created mouse models in which human tau protein accumulates in neurons, neurofibrillary tangles form, synaptic transmission is disrupted, memory and learning ability decrease. When the animals were 12 months old, which is equivalent to 60 years in humans, they were treated with zileuton, a drug that inhibits the synthesis of leukotrienes by blocking the enzyme 5–lipoxygenase.
After 16 weeks of treatment, the animals underwent tests in the maze to assess their memory and spatial learning. Compared with untreated animals, mice that received zileuton showed better results.
To determine the cause of this effect, the researchers analyzed the level of leukotrienes in the body of mice. They found that mice after taking zileuton had a 90% decrease in leukotrienes compared to untreated mice. In addition, the level of insoluble tau protein, which directly damages synapses, was 50% lower in animals from the experimental group. Microscopic examination revealed significant differences in the state of synapses in mice of different groups. While the control animals had a significant deterioration in synaptic transmission, the synapses of tau mice after receiving zileuton were indistinguishable from the synapses of normal mice of their age without the disease.
The study is interesting because zileuton has already been approved by the FDA for the treatment of bronchial asthma, so the results may soon be translated into clinical practice for the treatment of patients with Alzheimer's disease.
Article by P. F. Giannopoulos et al. Learning Impediments, Memory Deficits, and Neuropathology in Aged Tau Transgenic Mice Are Dependent on Leukotrienes Biosynthesis: Role of the cdk5 Kinase Pathway published in the journal Molecular Neurobiology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Temple Health: Temple Researchers Successfully Reverse Cognitive Impediments in Mice with Dementia.