Role of the mTOR pathway in animal models of genetic and acquired epilepsies

• Autorzy: Wong M.
• Języki publikacji: EN

Abstrakty

EN

Current medical treatments are ineffective in at least one-third of all epilepsy patients and do not have proven disease-modifying or antiepileptogenic properties for preventing the development or progression of epilepsy. While available antiseizure drugs act primarily by suppressing neuronal activity via modulation of ion channels and neurotransmitter systems, more effective, disease‑modifying therapies need to target novel mechanisms of action involved in the underlying process of epileptogenesis. The mechanistic target of rapamycin (mTOR) pathway represents a promising candidate for targeting anti-epileptogenic therapy. In the genetic disorder, tuberous sclero sis complex (TSC), epilepsy is very common and is often drug-resistant. The mTOR pathway has been strongly implicated in causing epileptogenesis in mouse models of TSC and mTOR inhibitors have both anti‑seizure effects in decreasing existing seizures and anti‑epileptogenic effects in preventing epilepsy in these models. Furthermore, there is evidence that the mTOR pathway may be involved in epileptogenesis in animal models of acquired epilepsy, such as following status epilepticus or traumatic brain injury. A number of downstream mechanisms have been implicated in mediating the effects of mTOR in epileptogenesis, including cell growth, synaptic plasticity, inflammation, neurogenesis, and translational regulation. This work in animal models has started to be translated to patients, as clinical trials of mTOR inhibitors for epilepsy in TSC patients are in progress.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.30

Twórcy

autor

Wong M.

• Department of Neurology, Washington University School of Medicine, St. Louis, USA