Progressive myoclonus epilepsy

Girard, Jean Marie; Turnbull, Julie; Ramachandran, N.; Minassian, Berge A.

doi:10.1016/b978-0-444-59565-2.00043-5

Cited by 38 publications

(27 citation statements)

References 35 publications

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“…The treatment of patients with progressive myoclonus epilepsies such as Lafora disease proves to be very difficult, and previously normal children or teenagers are afflicted with everworsening and soon-intractable myoclonus and epilepsy [40]. Case reports are suggesting efficacy of PER in progressive myoclonus epilepsies [10,41].…”

Section: Use In Progressive Myoclonus Epilepsiesmentioning

confidence: 99%

Perampanel in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus

Strzelczyk

Willems

Willig

et al. 2015

Expert Review of Clinical Pharmacology

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Perampanel is the latest approved antiepileptic drug in focal and generalized epilepsies and has a distinct and selective mode of action on AMPA-receptors. Several thousand patients have received perampanel within randomized placebo-controlled trials, open-label extension trials and post-marketing observational studies. Significant median partial-onset seizure reduction rates of 23% for 4 mg/day, 26-31% for 8 mg/day and 18-35% for 12 mg/day were reported. Likewise 50 percent responder rates were 29% for 4 mg/day, 33-38% for 8 mg/day and 34-36% for 12 mg/day. Primary generalized tonic-clonic seizures were reduced by 76.5% (8 mg) vs 38.4% (placebo) in a recent controlled trial. Overall, perampanel is well tolerated and the main adverse events are dizziness, somnolence and fatigue. There are also anecdotal reports on use in progressive myoclonic epilepsies and status epilepticus. Perampanel will likely remain an important, possibly broad-spectrum AED with a significant market share, especially in patients with drug-refractory epilepsies.

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Section: Use In Progressive Myoclonus Epilepsiesmentioning

confidence: 99%

Perampanel in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus

Strzelczyk

Willems

Willig

et al. 2015

Expert Review of Clinical Pharmacology

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“…For example, there are many factors that determine the stability of network connectivity, including the survival of neurons, that may be linked to epilepsy. As an example, the intractable epilepsies associated with neurodegenerative diseases 81 such as the neuronal ceroid lipofuscinoses 82 can be most readily explained as network instabilities engendered by loss of connectivity, including loss of neurons. Thus the molecular mechanisms of the epilepsies may be considered as a diverse set of pathways leading to a final common pathophysiology of a self-reinforcing cycle of activity-dependent disinhibition.…”

Section: Neuronal Homeostasis Gone Awrymentioning

confidence: 99%

Molecular mechanisms of epilepsy

2015

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Decades of experimental work have established an imbalance of excitation and inhibition as the leading mechanism of the transition from normal brain function to seizure. In epilepsy, these transitions are rare and abrupt. Transition processes incorporating positive feedback, such as activity-dependent disinhibition, could provide these unique timing features. A rapidly expanding array of genetic etiologies will help delineate the molecular mechanism(s). This delineation will entail quite a bit of cell biology. The genes discovered to date are currently more remarkable for their diversity than their similarities.

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“…Of interest, mutations in Laforin have been associated with the abnormal accumulation of glycogen in Lafora disease [18]. This includes a W32G mutation in the CBM20 of Laforin [19].…”

Section: Introductionmentioning

confidence: 99%

The carbohydrate-binding domain of overexpressed STBD1 is important for its stability and protein–protein interactions

et al. 2014

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STBD1 (starch-binding domain-containing protein 1) belongs to the CBM20 (family 20 carbohydrate binding module) group of proteins, and is implicated in glycogen metabolism and autophagy. However, very little is known about its regulation or interacting partners. Here, we show that the CBM20 of STBD1 is crucial for its stability and ability to interact with glycogen-associated proteins. Mutation of a conserved tryptophan residue (W293) in this domain abolished the ability of STBD1 to bind to the carbohydrate amylose. Compared with the WT (wild-type) protein, this mutant exhibited rapid degradation that was rescued upon inhibition of the proteasome. Furthermore, STBD1 undergoes ubiquitination when expressed in COS cells, and requires the N-terminus for this process. In contrast, inhibition of autophagy did not significantly affect protein stability. In overexpression experiments, we discovered that STBD1 interacts with several glycogen-associated proteins, such as GS (glycogen synthase), GDE (glycogen debranching enzyme) and Laforin. Importantly, the W293 mutant of STBD1 was unable to do so, suggesting an additional role for the CBM20 domain in protein–protein interactions. In HepG2 hepatoma cells, overexpressed STBD1 could associate with endogenous GS. This binding increased during glycogenolysis, suggesting that glycogen is not required to bridge this interaction. Taken together, our results have uncovered new insights into the regulation and binding partners of STBD1.

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Progressive myoclonus epilepsy

Cited by 38 publications

References 35 publications

Perampanel in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus

Perampanel in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus

Molecular mechanisms of epilepsy

The carbohydrate-binding domain of overexpressed STBD1 is important for its stability and protein–protein interactions

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