Epilepsy and Alzheimer's: the nasal spray must protect against seizures
An American research team has developed a new peptide that supports the natural mechanism by which the brain prevents seizures based on an overreaction of neurons. Such seizures are particularly common in Alzheimer's disease or epilepsy. The peptide can be administered via a nasal spray.
Researchers from the Medical College of Georgia at the University of Augusta (USA) present a nasal spray peptide that can reduce sensitivity to uncontrolled electrical activity in the brain and thus protect against Alzheimer's attacks and 'epilepsy. The research results were recently presented in the journal "JCI Insight".
A new peptide soothes the brain
According to the study, the peptide, called A1R-CT, is able to calm neuron activity in the brain that has gone out of control. Such overreactions are especially common after traumatic brain injuries and strokes. More than 60 percent of all people affected by Alzheimer's disease suffer from such attacks.
Since the peptide can be administered quickly and easily through the nose, it could also be suitable as a new drug for the treatment of acute attacks.
How does the A1R-CT peptide work?
As the working group explains, the peptide inhibits a protein called neurabine. This occurs primarily in the brain and is actually responsible for preventing overactivity of the so-called adenosine-1 receptor.
What does the adenosine 1 receptor do?
"This is a powerful receptor that silences neurons," says Professor Dr. Qin Wang of the research team. If the A1 receptor is over-activated, we fall asleep, explains the lead scientist. According to her, for example, caffeine is a substance that blocks the A1 receptor and thus prevents falling asleep.
“Neurons try to make sure everything stays under control, and for most of us that works pretty well,” Dr. Wang explains further. This way we don't just fall asleep at a desk, for example, or have uncontrolled seizures.
In Alzheimer's disease, communication in the brain is disrupted
However, in the brain of people with Alzheimer's disease, communication between neurons is disrupted by the characteristic accumulation of amyloid and tau proteins. This can lead to stress reactions in the brain, resulting in excessive excitation of neurons.
The researchers therefore consider the A1 receptor, activated by the molecule adenosine, which is very widespread in the body, as a promising therapeutic target for calming neuronal hyperactivity.
The A1 receptor is widespread in the body
The only problem is that A1 is distributed throughout the body, including the heart, lungs, and kidneys. A drug that directly targets the A1 receptor would therefore likely cause widespread side effects throughout the body.
Neurabin controls the A1 receptor in the brain
As Wang's work group discovered, the protein neurabine, which is used for targeted control of the A1 receptor in the brain, also appears to be found primarily in the brain. Therefore, the team developed a peptide that inhibits neurabine instead of directly interacting with the A1 receptor.
"The fact that neurabine is found primarily in the brain means that altering its activity should not have the potential effects throughout the body that directly altering A1 receptor activity would have," Wang confirms.
Hyperpolarization of neurons
By inhibiting neurabine, the A1 receptors in the brain are further activated. As a result, the excitation state of neurons is attenuated. Researchers call this mechanism hyperpolarization. This means that neurons are less likely to emit an electrical signal.
A1R-CT peptide may prevent severe seizures
In a mouse model, the working group has already demonstrated that the A1R-CT peptide can prevent severe epileptic seizures and seizures typical of Alzheimer's disease by inhibiting neurabine.
Tests on mice also showed that the peptide had a similar effect when given via a nasal spray as when injected directly into the brain. This greatly increases the potential clinical benefit of the peptide.
The peptide must now be tested on humans
The next step is to test the peptide on humans. For this purpose, it must first be determined for the individual clinical pictures in which the clinical use of the agent is possible, what dose should be administered and at what time in order to achieve the optimal result. (vb)
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This text corresponds to the specifications of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.
Graduate editor (FH) Volker Blasek
Sources:Medical College of Georgia: Nasal Spray Peptide May Reduce Seizure Activity, Protect Neurons in Alzheimer's Disease, Epilepsy (Published: 2022/08/16), eurekalert.orgShalini Saggu, Yunjia Chen, Qin Wang, et al. : A Peptide Blocking the ADORA1-Neurabin Interaction Is Anticonvulsant and Inhibits Epilepsy in a Model of Alzheimer's; in: JCI Insight (2022), ncbi.nlm.nih.gov
This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.