Targeting LDH enzymes with a stiripentol analog to treat epilepsy

@article{Sada2015TargetingLE,
  title={Targeting LDH enzymes with a stiripentol analog to treat epilepsy},
  author={Nagisa Sada and Suni Lee and Takashi Katsu and Takemi Otsuki and Tsuyoshi Inoue},
  journal={Science},
  year={2015},
  volume={347},
  pages={1362 - 1367}
}
Targeting metabolism to tackle seizures About 1% of us suffer from epilepsy. Unfortunately, presently available drugs do not work for a third of epileptic patients. Sada et al. wanted to develop compounds to treat drug-resistant epilepsy (see the Perspective by Scharfman). They focused on a metabolic pathway in the brain, the astrocyte-neuron lactate shuttle. They found that lactate dehydrogenase, a key molecule in nerve cell metabolism, controls brain excitability. Searching for a substance… 
Commentary: Targeting LDH enzymes with a stiripentol analog to treat epilepsy
  • C. Cho
  • Biology
    Front. Cell. Neurosci.
  • 2015
TLDR
Lactate is released from astrocytes through monocarboxylate transporters (MCT1 and MCT4), and has been also reported to be released through ion channels yet to be identified (Korn et al., 2005, 2015).
Upregulation of lactate dehydrogenase A in a chronic model of temporal lobe epilepsy
TLDR
It is shown that chronic seizures increase LDHA, and conversely, the inhibition of LDHA suppresses seizures, which supports LDHA as a molecular target for the development of new antiepileptic drugs.
Metabolic Control of Epilepsy: A Promising Therapeutic Target for Epilepsy
Epilepsy is a common neurological disease that is not always controlled, and the ketogenic diet shows good antiepileptic effects drug-resistant epilepsy or seizures caused by specific metabolic
Metabolic Control of Epilepsy: A Promising Therapeutic Target for Epilepsy
TLDR
Regulation of neuronal excitation via metabolic pathways and antiepileptic therapies targeting metabolic pathways are emphasized to provide insight into the state of the art concerning the brain’s metabolic patterns and their association with epilepsy.
The metabolic basis of epilepsy
TLDR
Evidence that supports both pathophysiological and therapeutic roles for brain metabolism in epilepsy is reviewed, highlighting the growing recognition that disruptions in cellular metabolism can be both a cause and a consequence of epileptic seizures and how this emerging science might be exploited to develop innovative therapeutic strategies.
Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters
TLDR
The results suggest that MCTs not only play an important role in the transport of ketone bodies, but also in the modulation of brain energy metabolism under normal and ketogenic conditions.
Hungry Neurons: Metabolic Insights on Seizure Dynamics
TLDR
This review summarizes the clinical and preclinical observations showing metabolic dysregulation during epileptogenesis, seizure initiation, and termination, and in the inter-ictal period and presents initial evidence for the effectiveness of 2-DG in arresting 4-Aminopyridine induced neocortical seizures in vivo in the mouse.
Use of the Ketogenic Diet to Treat Intractable Epilepsy in Mitochondrial Disorders
TLDR
The ketogenic diet and its more palatable formulations has shown promising results and is especially indicated and effective in the treatment of mitochondrial disorders due to complex I deficiency.
Neuregulin 1/ErbB4 signaling contributes to the anti-epileptic effects of the ketogenic diet
TLDR
A critical role of Nrg1/ErbB4 signaling in mediating KD’s effects on GABAergic activity and seizures is suggested, shedding light on developing new therapeutic interventions to seizure control.
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