New small protein drug may relieve stroke symptoms

Recently, in a new study published in "Science Advances", neuroscientists from the University of Pittsburgh Brain Research Institute discovered a new type of drug that can protect the brain during and after a stroke.

The study shows that damaged neurons can still survive if they do not have the biochemical pathway that causes the cell to enter death.

Anthony Schulien, the first author of the study and a graduate student at the Pittsburgh School of Medicine, said: "In clinical practice, no drug can prevent cell death after stroke. This study provides exciting early evidence for therapeutic targets. We hope that This evidence can be applied to patients in one day."

Elias Aizenman, a professor of neurobiology at the Pittsburgh School of Medicine and the corresponding author of the study, explained: “Stroke occurs because a blood clot blocks the blood vessels in the brain, preventing blood and oxygen from reaching the neurons, resulting in neuron death. Neighboring neurons in one In the area called the penumbra of stroke, even if their blood and oxygen supply is only slightly or temporarily reduced, they will become dysfunctional and will die within hours or days."

Aizenman said: "We are also looking for ways to prevent the death of other neurons. If we can do this, rehabilitation will be improved, and we can better help stroke patients to effectively intervene when they are unable to seek medical attention in time. With symptomatic drugs, we can also slow the progression of known strokes before the patient reaches the hospital."

In previously published research, Aizenman’s team’s research showed that the interaction between the cell membrane potassium channel protein Kv2.1 and the syntaxin protein would cause potassium ions to leak out of neurons, which would trigger cell death. They found that using an experimental compound called TAT-C1aB can prevent cell death by interfering with the interaction of syntaxin and Kv2.1.

In this new study, the researchers identified two types of Kv2.1 channels in neuronal cell membranes. One channel is usually related to cell excitability, while the other channel allows other new Kv2.1 channels to enter the cell membrane, thereby promoting the release of potassium and ultimately leading to neuronal cell death.

Armed with this knowledge, the researchers created a new small protein called TAT-DP-2, which can disrupt these new channels into the cell membrane, leaving potassium in the cell, thereby preventing the biochemical pathway of cell death.

Studies have shown that mice injected with TAT-DP-2 after stroke have a smaller stroke injury area and have better long-term neurological function than mice without injection (as shown in the figure below).

Aizenman said: "Two completely different methods using Kv2.1 can improve stroke outcomes, which shows the promise of neuroprotective drugs that target this channel."