MANTEGAZZA , Massimo

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Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures and EEG abnormalities on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both nongenetic and genetic etiologies. Genetic DEEs...

Dravet syndrome is caused mainly by mutations of voltage-gated Na(+) channels (most of them targeting Na(V) 1.1) and in few cases by mutations of γ-aminobutyric acid (GABA)(A) receptor γ2 subunit. In vitro functional analysis has provided important information about the pathogenic mechanism of these mutations, which is in most cases consistent...

Dravet syndrome is caused mainly by mutations of voltage-gated Na(+) channels (most of them targeting Na(V) 1.1) and in few cases by mutations of γ-aminobutyric acid (GABA)(A) receptor γ2 subunit. In vitro functional analysis has provided important information about the pathogenic mechanism of these mutations, which is in most cases consistent...

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Number of text pages 18 Number of words (summary) 184 Number of words (main text); 7620 Number of tables: 0 Number of figures: 1  SCN1A/NaV1.1 mutations are involved in different epilepsies and in familial hemiplegic migraine.  We have reviewed pathological mechanisms identified with experimental models, highlighting advantages, limits and...

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Number of text pages 18 Number of words (summary) 184 Number of words (main text); 7620 Number of tables: 0 Number of figures: 1  SCN1A/NaV1.1 mutations are involved in different epilepsies and in familial hemiplegic migraine.  We have reviewed pathological mechanisms identified with experimental models, highlighting advantages, limits and...

This scientific commentary refers to 'Gene variant effects across sodium channelopathies predict function and guide precision therapy' by Brunklaus et al. (https://doi.org/10.1093/brain/awac006).

This scientific commentary refers to 'Gene variant effects across sodium channelopathies predict function and guide precision therapy' by Brunklaus et al. (https://doi.org/10.1093/brain/awac006).

Voltage-gated sodium channels initiate action potentials in nerve, skeletal muscle, and other electrically excitable cells. Mutations in them cause a wide range of diseases. These channelopathy mutations affect every aspect of sodium channel function, including voltage sensing, voltage-dependent activation, ion conductance, fast and slow...

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Voltage-gated sodium channels (VGSCs) are key mediators of intrinsic neuronal and muscle excitability. Abnormal VGSC activity is central to the pathophysiology of epileptic seizures, and many of the most widely used antiepileptic drugs, including phenytoin, carbamazepine, and lamotrigine, are inhibitors of VGSC function. These antiepileptic...

Single-unit recordings performed in temporal lobe epilepsy patients and in models of temporal lobe seizures have shown that interneurons are active at focal seizure onset. We performed simultaneous patch-clamp and field potential recordings in entorhinal cortex slices of GAD65 and GAD67 C57BL/6J male mice that express green fluorescent protein...

Cortical spreading depression (CSD) is a wave of transient intense neuronal firing leading to a long lasting depolarizing block of neuronal activity. It is a proposed pathological mechanism of migraine with aura. Some forms of migraine are associated with a genetic mutation of the Nav1.1 channel, resulting in its gain of function and implying...

The persistent Na⁺ current (I(NaP)) is important for neuronal functions and can play a role in several pathologies, although it is small compared to the transient Na⁺ current (I(NaT)). Notably, I(NaP) is not a real persistent current because it undergoes inactivation with kinetics in the order of tens of seconds, but this property has often...

NaV1.1 (SCN1A) is a voltage-gated sodium channel mainly expressed in GABAergic neurons. Loss of function mutations of NaV1.1 lead to epileptic disorders, while gain of function mutations cause a migraine in which cortical spreading depolarizations (CSDs) are involved. It is still debated how these opposite effects initiate two different...

The persistent Na⁺ current (I(NaP)) is important for neuronal functions and can play a role in several pathologies, although it is small compared to the transient Na⁺ current (I(NaT)). Notably, I(NaP) is not a real persistent current because it undergoes inactivation with kinetics in the order of tens of seconds, but this property has often...

Mutations of genes coding for ion channels cause several genetically determined human epileptic syndromes. The identification of a gene variant linked to a particular disease gives important information, but it is usually necessary to perform functional studies in order to completely disclose the pathogenic mechanisms. The functional...

The nuclear receptor COUP TFI (also known as Nr2f1) plays major roles in specifying distinct neuronal subtypes during patterning of the neocortical motor and somatosensory cortex, as well as in regulating the longitudinal growth of the hippocampus during development. In humans, mutations in the NR2F1 gene lead to a global developmental delay...

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Mutations of genes coding for ion channels cause several genetically determined human epileptic syndromes. The identification of a gene variant linked to a particular disease gives important information, but it is usually necessary to perform functional studies in order to completely disclose the pathogenic mechanisms. The functional...