Last update 01 Nov 2024

CHRNB2 x CHRNA4

Last update 01 Nov 2024

Basic Info

Related Targets

CHRNB2CHRNA4

Drugs associated with CHRNB2 x CHRNA4

NESS 29-64FD

Target

CHRNA4 x CHRNB2

Mechanism

CHRNA4 modulators [+1]

Active Org.-

Originator Org.

PharmaNess Neuroscience

Active Indication-

Inactive Indication

Neurodegenerative Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CHRNB2 x CHRNA4

100 Translational Medicine associated with CHRNB2 x CHRNA4

0 Patents (Medical) associated with CHRNB2 x CHRNA4

Literatures (Medical) associated with CHRNB2 x CHRNA4

15 Aug 2024·Biology of Reproduction

Neonicotinoids differentially modulate nicotinic acetylcholine receptors in immature and antral follicles in the mouse ovary

Article

Author: Mourikes, Vasiliki E ; Deviney, Ashley ; Neff, Alison ; Flaws, Jodi A ; Laws, Mary J ; Santacruz-Márquez, Ramsés

AbstractNeonicotinoids are the most widely used insecticides in the world. They are synthetic nicotine derivatives that act as nicotinic acetylcholine receptor agonists. Although parent neonicotinoids have low affinity for the mammalian nicotinic acetylcholine receptor, they can be activated in the environment and the body to positively charged metabolites with high affinity for the mammalian nicotinic acetylcholine receptor. Imidacloprid, the most popular neonicotinoid, and its bioactive metabolite desnitro-imidacloprid differentially interfere with ovarian antral follicle physiology in vitro, but their effects on ovarian nicotinic acetylcholine receptor subunit expression are unknown. Furthermore, ovarian nicotinic acetylcholine receptor subtypes have yet to be characterized in the ovary. Thus, this work tested the hypothesis that ovarian follicles express nicotinic acetylcholine receptors and their expression is differentially modulated by imidacloprid and desnitro-imidacloprid in vitro. We used polymerase chain reaction, RNA in situ hybridization, and immunohistochemistry to identify and localize nicotinic acetylcholine receptor subunits (α2, 4, 5, 6, 7 and β1, 2, 4) expressed in neonatal ovaries (NO) and antral follicles. Chrnb1 was expressed equally in NO and antral follicles. Chrna2 and Chrnb2 expression was higher in antral follicles compared to NO and Chrna4, Chrna5, Chrna6, Chrna7, and Chrnb4 expression was higher in NO compared to antral follicles. The α subunits were detected throughout the ovary, especially in oocytes and granulosa cells. Imidacloprid and desnitro-imidacloprid dysregulated the expression of multiple nicotinic acetylcholine receptor subunits in NO, but only dysregulated one subunit in antral follicles. These data indicate that mammalian ovaries contain nicotinic acetylcholine receptors, and their susceptibility to imidacloprid and desnitro-imidacloprid exposure varies with the stage of follicle maturity.

01 Mar 2023·Pharmacological Research

Nicotinic acetylcholine receptors and epilepsy

Article

Author: Grandi, Laura Clara ; Becchetti, Andrea ; Cerina, Marta ; Amadeo, Alida

Despite recent advances in understanding the causes of epilepsy, especially the genetic, comprehending the biological mechanisms that lead to the epileptic phenotype remains difficult. A paradigmatic case is constituted by the epilepsies caused by altered neuronal nicotinic acetylcholine receptors (nAChRs), which exert complex physiological functions in mature as well as developing brain. The ascending cholinergic projections exert potent control of forebrain excitability, and wide evidence implicates nAChR dysregulation as both cause and effect of epileptiform activity. First, tonic-clonic seizures are triggered by administration of high doses of nicotinic agonists, whereas non-convulsive doses have kindling effects. Second, sleep-related epilepsy can be caused by mutations on genes encoding nAChR subunits widely expressed in the forebrain (CHRNA4, CHRNB2, CHRNA2). Third, in animal models of acquired epilepsy, complex time-dependent alterations in cholinergic innervation are observed following repeated seizures. Heteromeric nAChRs are central players in epileptogenesis. Evidence is wide for autosomal dominant sleep-related hypermotor epilepsy (ADSHE). Studies of ADSHE-linked nAChR subunits in expression systems suggest that the epileptogenic process is promoted by overactive receptors. Investigation in animal models of ADSHE indicates that expression of mutant nAChRs can lead to lifelong hyperexcitability by altering i) the function of GABAergic populations in the mature neocortex and thalamus, ii) synaptic architecture during synaptogenesis. Understanding the balance of the epileptogenic effects in adult and developing networks is essential to plan rational therapy at different ages. Combining this knowledge with a deeper understanding of the functional and pharmacological properties of individual mutations will advance precision and personalized medicine in nAChR-dependent epilepsy.

01 Apr 2022·Journal of Central Nervous System Disease

Sleep-related hypermotor epilepsy with genetic diagnosis: description of a case series in a tertiary referral hospital

Article

Author: Sánchez-García, Javier ; Caballero-Martínez, Manuel ; Arenas-Cabrera, Carmen ; Baena-Palomino, Pablo ; Chocrón-González, Yamin ; Oliver-Romero, María

Introduction Sleep-related hypermotor epilepsy (SHE) is characterized by asymmetric tonic/dystonic posturing and/or complex hyperkinetic seizures occurring mostly during sleep. Experts agree that SHE should be considered a unique syndrome. PURPOSE We present 8 cases of SHE for which a genetic diagnosis was carried out using a multigene epilepsy panel. Methods We retrospectively screened familial and isolated cases of SHE in current follow-ups in our center. Results We included 8 (5F/3M) patients, 5 of whom had a positive familial history of epilepsy. We identified a pathogenic mutation in CHRNA4, CHRNB2, and 3 different pathogenic changes in DEPDC5. Conclusions Awareness of SHE needs to be raised, given its implications for finding an appropriate treatment, its relationship to cognitive and psychiatric comorbidities, and the opportunity to prevent the disorder in the descendants. We present our series with their clinical, radiological, electroencephalographic, and genetic characteristics, in which we found 3 pathogenic mutations in the DEPDC5 gene but not previously reported in the literature. Identifying new pathogenic mutations or new genes responsible for SHE will facilitate a better understanding of the disease and a correct genetic counseling.

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