Abstract: Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na+-gated K+ channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have dierent roles in developing and mature brains. Under this respect, nicotinic receptors are paradigmatic, as dierent pathophysiological roles are exerted by distinct nAChR subunits in adult and developing brains. The widest evidence concerns 4 and 2 subunits. These participate in heteromeric nAChRs that are major modulators of excitability in mature neocortical circuits as well as regulate postnatal synaptogenesis. However, growing evidence implicates mutant 2 subunits in ADSHE, which poses interpretive diculties as very little is known about the function of 2-containing (2*) nAChRs in the human brain. Planning rational therapy must consider that pharmacological treatment could have dierent eects on synaptic maturation and adult excitability. We discuss recent attempts towards precision medicine in the mature brain and possible approaches to target developmental stages. These issues have general relevance in epilepsy treatment, as the pathogenesis of genetic epilepsies is increasingly recognized to involve developmental alterations.
Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy : Pathophysiology and Pharmacology / A. Becchetti, L.C. Grandi, G. Colombo, S. Meneghini, A. Amadeo. - In: BRAIN SCIENCES. - ISSN 2076-3425. - 10:12(2020 Nov), pp. 907.1-907.20.
|Titolo:||Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy : Pathophysiology and Pharmacology|
AMADEO, ALIDA (Ultimo)
|Parole Chiave:||autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE); autosomal dominant sleep-related hypermotor epilepsy (ADSHE); antiepileptic; cholinergic receptor nicotinic alpha 2 subunit (CHRNA2); cholinergic receptor nicotinic alpha 4 subunit (CHRNA4); cholinergic receptor nicotinic beta 2 subunit (CHRNB2); K+-Cl cotransporter type 2 (KCC2); neuronal nicotinic acetylcholine receptor (nAChR); synaptogenesis|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
Settore BIO/16 - Anatomia Umana
|Data di pubblicazione:||nov-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/brainsci10120907|
|Appare nelle tipologie:||01 - Articolo su periodico|