Nasal spray-releasing peptide reduces seizure activity, protects neurons in Alzheimer's disease, epilepsy

In research models of Alzheimer's disease and epilepsy, a novel peptide enhances the brain's natural mechanisms to help prevent epilepsy and protect neurons, scientists repor.

The scientists developed A1R-CT, said D.

The fact that it can be delivered through the nose suggests the peptide's potential as a new epilepsy-saving drug that could also help interrupt, for example, epilepsy clusters, where disabling epilepsy occurs in a row, said Wang, the journal's corresponding author at Johnson Controls of insigh.

A1R-CT works by inhibiting neuronal proteins, a protein that helps ensure that the protective mechanism itself doesn't become overexcited, she said, which inhibits neurons from overexciting, disrupting normal communication and preventing them from overexcitin.

The peptide is named for the protective adenosine receptor 1 on the surface of neurons, which is activated by adenosine, a type of glial cell that supports neurons primarily in the brain in response to hyperexcitability produced chemical.

"It's a powerful receptor that can silence neurons," Wang sai.

"But the A1 receptor itself has to be regulated, because if it's overactivated, you fall asleep," Wang sai.

Alzheimer's often accompanies seizures because the characteristic buildup of amyloid and tau proteins in the brain disrupts communication between neurons, creating increased oxidative stress and leading to inflammation, contributing to altered dynamics, she sai.

A1 receptors are activated by adenosine in this hyperactive condition, which seems to be a logical therapeutic target for seizure.

Going back to the neuron's desire for homeostasis, Wang and her colleagues discovered neuronal proteins, which appear to be found primarily in the brain, to provide this balance to prevent overactivity of A1 receptor.

The neurobin resides primarily in the brain, which means altering its activity doesn't have the potential to affect the whole body as directly altering A1 receptor activity, Wang sai.

"Neurabin is a brake, so it doesn't do much," Wang sai.

So they set out to develop a peptide that could interfere with the interaction of A1 receptors and neurotin, resulting in more natural protective, seizure-reducing benefit.

Activation of A1 receptors inhibits the excitatory state of neurons by regulating ion channels (proteins on the cell membrane that allow other proteins to pass through the cell), which help generate electrical signal.

Activation of A1 receptors also reduces the release of glutamate, a neurotransmitter produced by neurons that excites the.

Now, they have shown that inhibiting neuroside, either directly or through its peptides, increases the action of A1C, thereby reducing excessive electrical activity in the brai.
They have shown that the peptide is effective in both a mouse model of severe epilepsy and a mouse model of Alzheimer's diseas.
It is effective when injected directly into the brain or via a nasal spra.

The scientists chose to observe nasal spray delivery to fully explore the potential clinical benefit of the peptid.
They found similarly robust responses in models of epilepsy and Alzheimer's diseas.

Looking further into the effects of neuron targeting, they found that neuron-deficient mice had significantly shorter and lighter seizures, and all survive.
Those with normal neurotin levels experienced seizures for up to 30 minutes, and about 10 percent died shortly thereafte.
Blocking the A1 receptor caused more severe seizures in neuron-deficient mice and increased mortality to more than 50 percen.

Next steps include additional exploration of ideal doses and delivery times, where the peptide might be used therapeuticall.

The scientific team is also continuing to tweak the peptide to ensure it functions optimally and is seeking the funding needed to conduct clinical trial.

Wang, a Georgia Research Alliance Distinguished Scholar, came to MCG in April 2021 from the University of Alabama at Birmingham, where she began research on A1 receptors and peptide developmen.
She continues to collaborate extensively on research with her colleagues at UAB, who are co-authors of the new pape.
First author Shalini Saggu, PhD, is also now a faculty member in MCG's Department of Neuroscience and Regenerative Medicin.

Seizures are common after traumatic brain injury; stroke, thought to be an acquired brain injury; and chronic neurodegenerative diseases, including Alzheimer'.

As many as 64 percent of the roughly 50 million Alzheimer's patients experience seizures, the scientists wrot.
Patients may have generalized tonic-clonic seizures in which they fall, tremble, and become unresponsiv.
Also, focal seizures tend to be shorter and may include repetitive movements of the arms or legs, smacking, and chewin.

About 40 percent of people have uncontrolled seizures, the scientists wrote, demonstrating the urgent need for new treatments, which tend to be less effective in Alzheimer's patient.
If uncontrolled, epilepsy can cause brain damage and cognitive impairmen.

Adenosine is also a building block of our DNA and a component of ATP, the fuel for cell.

This research was supported by the National Institutes of Healt.

article title

Peptides that block ADORA1-neurabin interaction have anticonvulsant and epilepsy inhibitory effects in Alzheimer's disease models