Asset Details
Do you wish to reserve the book?
Hyperactivity of mTORC1 and mTORC2-dependent signaling mediate epilepsy downstream of somatic PTEN loss
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Hyperactivity of mTORC1 and mTORC2-dependent signaling mediate epilepsy downstream of somatic PTEN loss
Do you wish to request the book?
Hyperactivity of mTORC1 and mTORC2-dependent signaling mediate epilepsy downstream of somatic PTEN loss
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Paper
Hyperactivity of mTORC1 and mTORC2-dependent signaling mediate epilepsy downstream of somatic PTEN loss
2024
Overview
Gene variants that hyperactivate PI3K-mTOR signaling in the brain lead to epilepsy and cortical malformations in humans. Some gene variants associated with these pathologies only hyperactivate mTORC1, but others, such as PTEN, PIK3CA, and AKT, hyperactivate both mTORC1- and mTORC2-dependent signaling. Previous work established a key role for mTORC1 hyperactivity in mTORopathies, however, whether mTORC2 hyperactivity contributes is not clear. To test this, we inactivated mTORC1 and/or mTORC2 downstream of early Pten deletion in a new model of somatic Pten loss-of-function (LOF) in the cortex and hippocampus. Spontaneous seizures and epileptiform activity persisted despite mTORC1 or mTORC2 inactivation alone, but inactivating both mTORC1 and mTORC2 simultaneously normalized brain activity. These results suggest that hyperactivity of both mTORC1 and mTORC2 can cause epilepsy, and that targeted therapies should aim to reduce activity of both complexes.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Added additional data, data tables, and methods details. Improved figure images to better illustrate findings.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
Subject
