Qin Wang, neuropharmacologist and founding director of the Program for Alzheimer’s Therapeutics Discovery at the Medical College of Georgia at Augusta University.The fact that it can be delivered through the nose indicates the peptide’s potential as a new seizure rescue medication as well, to help interrupt, for example, a seizure cluster, where disabling seizures are occurring back-to- back, says Wang, corresponding author of the study in the journal JCI Insight.“This is a powerful receptor to then silence the neurons,” Wang says.Alzheimer’s often is accompanied by seizures because the characteristic buildup of the proteins amyloid and tau in the brain disrupts communication between neurons, creates increased oxidative stress and resulting inflammation, and in response to the altered dynamic, neurons can become hyperexcited, she says.“In Alzheimer’s there are so many things that go wrong,” she says.
Seizures can precede the cognitive decline in Alzheimer’s, and definitely contribute to it, Wang says.The fact neurabin is primarily in the brain, means that altering its activity should not have the potential body-wide impact of directly altering A1 receptor activity, Wang says.
The scientists have noted a dramatic reduction in death of neurons in their Alzheimer’s model, for example, with the use of their peptide.Now they’ve shown that inhibiting neurabin — either by reducing it directly or with their peptide — enables increased action by A1C to reduce excessive electrical activity in the brain.
They’ve shown the peptide is effective in both a mouse model of severe seizures and seizures in an Alzheimer’s mouse model.
And It’s effective when directly injected into the brain or via nasal spray.Epileptic seizures are common after a traumatic brain injury; a stroke, which is considered an acquired brain injury; and with chronic neurodegenerative diseases including Alzheimer’s.
“A peptide blocking the ADORA1-neurabin interaction is anticonvulsant and inhibits epilepsy in an Alzheimer’s model” by Qin Wang et al.A peptide blocking the ADORA1-neurabin interaction is anticonvulsant and inhibits epilepsy in an Alzheimer’s modelEpileptic seizures are common sequelae of stroke, acute brain injury, and chronic neurodegenerative diseases, including Alzheimer’s disease (AD), and cannot be effectively controlled in approximately 40% of patients, necessitating the development of novel therapeutic agents
We developed a peptide that blocks the A1R-neurabin interaction to enhance A1R activityFurthermore, in an AD mouse model with spontaneous seizures, nasal delivery of this blocking peptide reduces epileptic spike frequency
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