11 June 2021

Anti-stroke protein

Chinese scientists have developed a protein to protect neurons in stroke

Anastasia Kuznetsova, N+1

Chinese scientists have developed the protein Tat-CIRP, which protects neurons during stroke. They injected it into mice and rhesus monkeys and observed a decrease in the volume of the affected area and a decrease in neurological deficit. The positive effect was maintained if Tat-CIRP was administered both immediately after the stroke and after 6 hours. The study was published in Science Translational Medicine (Fang et al., An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke).

Every year in the world, stroke occurs in 16.9 million people, it accounts for 10 percent of the total mortality in the world. The only possible pharmacological treatment for stroke is the use of thrombolysis for 4.5 hours. Only 4-7 percent of patients get into this therapeutic window, the rest do not have time to receive thrombolysis due to delays in computed tomography or magnetic resonance imaging. Scientists are in a continuous search for drugs that have a neuroprotective effect, but so far success in treating animals has not been transferred to humans.

In ischemic and hemorrhagic strokes, cells die as a result of apoptosis (disintegration into separate apoptotic corpuscles) and necroptosis (necrotic death). Toll-like receptor 4 (TLR4) is involved in both processes, and mice that do not express it tolerate stroke better. Myeloid differentiation factor is required to activate TLR4 2 (MD2). Scientists hypothesized that by preventing the formation of the TLR4 complex with MD2, it is possible to reduce the number of cells that have undergone apoptosis and necroptosis.

A group of researchers led by Lize Xiong from Xijing Hospital in Xi'an has developed the protein Tat-CIRP. The SIRP domain binds MD2 with high specificity and prevents the formation of a TLR4 complex with MD2. The Tat domain facilitates penetration through the hemato-encephalic barrier. To study how effectively the Tat-CIRP protein reduces the effects of stroke, it was injected intravenously into mice immediately after the stroke, 6 hours later and a day later (the authors do not specify the number of mice in the groups). Tat-CIRP reduced neurological deficit and stroke area volume in a dose-dependent form (p<0.01).


The dose-dependent effect of Tat-CIRP. Figures from the article by Fang et al.

If Tat-CIRP was administered 3 or 6 hours after a stroke, its positive effect remained (p<0.05), and when administered after 9 hours it disappeared.


The effect of Tat-CIRP depends on the time of administration.

Scientists have also induced stroke in mice that do not produce the MD2 protein. In these animals, the brain was damaged to a lesser extent than in mice with functioning MD2. Then the mice with missing MD2 were injected with Tat-CIRP, but the researchers did not notice an improvement in their conditions. This proves that the Tat-CIRP effect is associated with MD2 blocking.

The researchers injected the Tat-CIRP protein to rhesus monkeys after a stroke (6 animals in the experimental protein group and 6 animals in the control group), and they also observed a decrease in the volume of the stroke zone and neurological deficit.


The effect of the introduction of Tat-CIRP after a stroke in macaques.

Scientists conclude that the developed protein inhibits apoptosis and necroptosis, and also has a long-term neuroprotective effect in mice and rhesus monkeys. Tat-CIRP is a good candidate for the role of neuroprotector in hemorrhagic and ischemic strokes, but now studies of its safety and effectiveness need to be conducted in humans.

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