Α7 AChRs Research Articles

Agonists or positive allosteric modulators of α7 nicotinic acetylcholine receptor prevent interaction of SARS-Cov-2 receptor-binding domain with astrocytoma cells

SARS-Cov-2, the virus causing COVID-19, penetrates host target cells via the receptor of angiotensin-converting enzyme 2 (ACE2). Disrupting the virus interaction with ACE2 affords a plausible mechanism for prevention of cell penetration and inhibiting dissemination of the virus. Our studies demonstrate that ACE2 interaction with the receptor binding domain of SARS-Cov-2 spike protein (RBD) can be impaired by modulating the α7 nicotinic acetylcholine receptor (α7 nAChR) contiguous with ACE2. U373 cells of human astrocytoma origin were shown to bind both ACE2-specific antibody and recombinant RBD in Cell-ELISA. ACE2 was found to interact with α7 nAChR in U373 cell lysates studied by Sandwich ELISA. Our studies demonstrate that inhibition of RBD binding to ACE2-expressing U373 cells were defined with α7 nAChR agonists choline and PNU282987, but not a competitive antagonist methyllicaconitine (MLA). Additionally, the type 2 positive allosteric modulator (PAM2) PNU120596 and hydroxyurea (HU) also inhibited the binding. Our studies demonstrate that activation of α7 AChRs has efficacy in inhibiting the SARS-Cov-2 interaction with the ACE2 receptor and in such a way can prevent virus target cell penetration. These studies also help to clarify the consistent efficacy and positive outcomes for utilizing HU in treating COVID-19.

Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications.

While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine other potential interactions between the virus and other cell receptors. Based on the clinical observation of low prevalence of smoking among hospitalized COVID-19 patients, we examined and identified a “toxin-like” amino acid (aa) sequence in the Receptor Binding Domain of the Spike Glycoprotein of SARS-CoV-2 (aa 375–390), which is homologous to a sequence of the Neurotoxin homolog NL1, one of the many snake venom toxins that are known to interact with nicotinic acetylcholine receptors (nAChRs). We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein and the superposition of the modelled structure of the Neurotoxin homolog NL1 and the SARS-CoV-2 Spike Glycoprotein. We also performed computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 Spike Glycoprotein and the extracellular domain of the nAChR α9 subunit. We identified a main interaction between the aa 381–386 of the SARS-CoV-2 Spike Glycoprotein and the aa 189–192 of the extracellular domain of the nAChR α9 subunit, a region which forms the core of the “toxin-binding site” of the nAChRs. The mode of interaction is very similar to the interaction between the α9 nAChR and α-bungarotoxin. A similar interaction was observed between the pentameric α7 AChR chimera and SARS-CoV-2 Spike Glycoprotein. The findings raise the possibility that SARS-CoV-2 may interact with nAChRs, supporting the hypothesis of dysregulation of the nicotinic cholinergic system being implicated in the pathophysiology of COVID-19. Nicotine and other nicotinic cholinergic agonists may protect nAChRs and thus have therapeutic value in COVID-19 patients.

A turripeptide from Polystira nobilis venom inhibits human α3β2 and α7 nicotinic acetylcholine receptors

Almost all marine snails within superfamily Conoidea produce venoms containing numerous neuroactive peptides. Most toxins characterized from members of this superfamily are produced by species belonging to family Conidae. These toxins (conotoxins) affect diverse membrane proteins, such as voltage- and ligand-gated ion channels, including nicotinic acetylcholine receptors (nAChRs). Family Turridae has been considerably less studied than their Conidae counterpart and, therefore, turrid toxins (turritoxins) have just been barely described. Consequently, in this work the most prominent chromatographic (RP-HPLC) fractions from the East Pacific species Polystira nobilis venom duct extract were isolated. The biological activity of six selected fractions was assayed on human (h) α7 AChRs expressed in Xenopus laevis oocytes. One of these fractions, F21, inhibited the acetylcholine-elicited response by 62 ± 12%. Therefore, this fraction was further purified and the F21-2 peptide was obtained. This peptide (at 5.6 μM) strongly and irreversibly inhibited the acetylcholine-induced response on hα7 and hα3β2 nAChRs, by 55 ± 4 and 91 ± 1%, respectively. Electrospray mass spectrometry indicates that the average molecular mass of this toxin is 12 358.80 Da. The affinity for hα3β2 nAChRs is high (IC50 of 566.2 nM). A partial sequence without cysteines was obtained by automated Edman degradation: WFRSFKSYYGHHGSVYRPNEPNFRSFAS…; blastp search revealed that this sequence has low similarity to some non-Cys-containing turripeptides. This is the first report of a turritoxin from a species of the American Pacific and the second description of a turripeptide inhibiting nAChRs.

PNU-120596, a positive allosteric modulator of mammalian α7 nicotinic acetylcholine receptor, is a negative modulator of ligand-gated chloride-selective channels of the gastropod Lymnaea stagnalis.

Excitatory α7 neuronal nicotinic receptors (nAChR) are widely expressed in the central and peripheral nervous and immune systems and are important for learning, memory, and immune response regulation. Specific α7 nAChR ligands, including positive allosteric modulators are promising to treat cognitive disorders, inflammatory processes, and pain. One of them, PNU-120596, highly increased the neuron response to α7 agonists and retarded desensitization, showing selectivity for α7 as compared to heteromeric nAChRs, but was not examined at the inhibitory ligand-gated channels. We studied PNU-120596 action on anion-conducting channels using voltage-clamp techniques: it slightly potentiated the response of human glycine receptors expressed in PC12 cells, of rat GABAA receptors in cerebellar Purkinje cells and mouse GABAA Rs heterologously expressed in Xenopus oocytes. On the contrary, PNU-120596 exerted an inhibitory effect on the receptors mediating anion currents in Lymnaea stagnalis neurons: two nAChR subtypes, GABA and glutamate receptors. Acceleration of the current decay, contrary to slowing down desensitization in mammalian α7 nAChR, was observed in L. stagnalis neurons predominantly expressing one of the two nAChR subtypes. Thus, PNU-120596 effect on these anion-selective nAChRs was just opposite to the action on the mammalian cation-selective α7 nAChRs. A comparison of PNU-120596 molecule docked to the models of transmembrane domains of the human α7 AChR and two subunits of L. stagnalis nAChR demonstrated some differences in contacts with the amino acid residues important for PNU-120596 action on the α7 nAChR. Thus, our results show that PNU-120596 action depends on a particular subtype of these Cys-loop receptors.

Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia

Dynorphin A is increased in neuropathic pain models. Activation of α7 n acetylcholine receptor (nAchR) reduces inflammation and pain. Whether activation of α7 nAchR affects dynorphin A release is unknown. The experiments evaluated the proinflammatory effect of dynorphin A in the spinal nerve ligation-induced neuropathic pain models and the effect of α7 nAchR activation on the dynorphin A content. α7 nAchR agonist, PHA-543613 and its antagonist, methyllycaconitine citrate were used and dynorphin A content was measured after spinal nerve ligation and in microglia cultures to test the analgesic mechanisms of α7 nAchR activation. The results showed that dynorphin A content peaked 3 to 7 days after nerve injury, and dynorphin A anti-serum intrathecal injection decreased IL-β and TNF-α content a week after nerve injury. Activation of α7 nAchR by PHA-543613 alleviated neuropathic pain behaviors and decreased dynorphin A concentration in the ipsilateral spinal cords. Also, PHA-543613 decreased dynorphin A release from the microglia cultures to LPS stimulation by activation of α7 nAchR. Our results suggest that dynorphin A contribute to the development and maintenance of neuropathic pain and that decreasing dynorphin A content by activation of α7 AchR of microglia is a potential therapeutic target for treating neuropathic pain.

Angiogenesis modulation by nicotine and nicotinic ligands

Nicotine, one of the thousands of chemicals in cigarette smoke has a highly debated effect on cell proliferation and tissue healing. Recent studies documented its pro-angiogenesis effects by stimulating endothelial cell α7 non-neronal nicotinic acetylcholine receptors (α7 AChR). Angiogenesis is a critical physiological process for cell survival and development. Endothelial cells, necessary for the course of angiogenesis, express several non-neuronal AChRs. The most important functional non-neuronal AChRs are homomeric α7 AChRs and several heteromeric AChRs formed by a combination of α3, α5, β2, and β4 subunits, including α3β4-containing AChRs. In endothelial cells, α7 AChR stimulation indirectly triggers the activation of the integrin ανβ 3 receptor and an intracellular MAP kinase (ERK) pathway that mediates angiogenesis. Non-selective cholinergic agonists such as nicotine have been shown to induce angiogenesis, enhancing tumor progression. Moreover, α7 AChR selective antagonists such as α-bungarotoxin and methyllycaconitine as well as the nonspecific antagonist mecamylamine have been shown to inhibit endothelial cell proliferation and ultimately blood vessel formation. Exploitation of such pharmacologic properties can lead to the discovery of new specific cholinergic antagonists as anti-cancer therapies. Conversely, the pro-angiogenic effect elicited by specific agonists can be used to treat diseases that respond to re-vascularization such as diabetic ischemia and atherosclerosis, as well as to accelerate wound healing. In this review we discuss the pharmacological evidence supporting the importance of non-neuronal AChRs in angiogenesis and potential intracellular mechanisms by which α7 AChR activation mediates these cellular processes.

The antidepressant-like activity of nicotine, but not of 3-furan-2-yl-N-p-tolyl-acrylamide, is regulated by the nicotinic receptor β4 subunit

The current study compares the antidepressant-like effect elicited by nicotine between wild-type (β4+/+) and knockout (β4−/−) mice, and subsequently, the effect of 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a positive allosteric modulator of α7 nicotinic receptors, on the previously determined activity of nicotine. Mice from each sex were injected daily with nicotine base (0.2 mg/kg; s.c.) or co-administered with PAM-2 (1.0 mg/kg; i.p.) for 3 weeks. Forced swim tests were performed to determine the acute (day 1), subchronic (day 7), and chronic (days 14 and 21) effects of the drugs, as well as their residual effects after treatment cessation (days 28 and 35). Our results indicate that nicotine mediates antidepressant-like activity after acute, subchronic, and chronic treatments in β4+/+, but not β4−/−, mice, and that these effects are not mediated by unspecific locomotor stimulation. Nicotine co-administered with PAM-2 produces antidepressant-like activity in both β4+/+ and β4−/− mice, except after the acute treatment of β4−/− mice, and decreases locomotor activity. This suggests that although the β4 subunit regulates the antidepressant-like activity of nicotine it does not affect the activity elicited by PAM-2 when is co-administered with nicotine. The residual antidepressant-like activity of PAM-2 + nicotine was observed only in female mice, suggesting gender-specific differences. Our findings clearly indicate that β4-containing nAChRs play an important role in the antidepressant-like activity elicited by nicotine but they are not essential for the modulatory activity of PAM-2. In fact, PAM-2 inhibits α4β4 and α3β4 AChRs at higher concentration ranges compared to that for the PAM activity previously found at the α7 AChR.

Studying α7 nicotinic receptor anti‐inflammatory signaling

α7 nicotinic receptors (α7 AChRs) reportedly play anti‐inflammatory roles in innate immune function, in part by blocking the transcription factor NFkB. We tested whether heterologously expressed α7 AChRs directly interact with NFkB signaling in the rat pituitary cell line GH3. GH3 cells show significant 125I‐α‐bungarotoxin (BT) binding when transfected with rat α7 nAChR, but in our hands, commercially available α7 antibodies do not detect α7 AChR in these transfected cells. For instance, α7 AChR‐GFP chimeras transfected into cells show BT binding, and anti‐GFP staining, but not anti‐α7 AChR staining in Western blots. Upon transfection with an NFkB promoter driving secreted alkaline phosphatase (NFkB‐SEAP), GH3 cells show up to 30 fold increases in SEAP secretion following 1‐100 ng/ml rat tumor necrosis factor (TNF) treatment. Nicotine (100 ‐1000 μM) and the selective α7 AChR agonist PNU282987 (PNU, 50‐300 μM) blocked TNF‐stimulated SEAP secretion in GH3 cells transfected with NFkB‐SEAP alone, while GTS21 did not. This suggests some nicotinic compounds have direct effects on NFkB signaling in non‐immune cells, since transfection with α7 had no further effect. To understand whether reported α7 AChR anti‐inflammatory effects are cell‐type dependent, we investigated α7 AChR drug effects in macrophage‐like cells (RAW 264.7 cells) using PNU, GTS21 and nicotine following lipopolysaccharide (LPS) stimulation (10 ng/ml). GTS21 (50‐200 µM) blocked LPS‐induced TNF release from RAW cells, but nicotine and PNU did not. Our findings suggest that α7 AChR do not directly interact with and subsequently block NFKB signaling, and that additional factors are required in heterologous cells to mimic the reported α7 AChR‐mediated anti‐inflammatory effects in immune cells.

Antidepressant activity in mice elicited by 3-furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor

The objective of the current study is to determine whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a positive allosteric modulator of α7 nicotinic receptors (AChRs), produces antidepressant-like behavior in mice, and reactivates desensitized α7 AChRs expressed in CH3-α7 cells. Mice from both sexes were injected (i.p.) with PAM-2 (1.0mg/kg) on a daily basis for three weeks. Forced swim tests (FSTs) were performed on Day 1 and Day 7 to determine the acute and subchronic effects of PAM-2, respectively, and on Days 14 and 21 to determine its chronic activity. To examine the residual effects after drug treatment, a withdrawal period of two more weeks was continued with FSTs performed on Day 28 and 35. Our results indicate that: (1) PAM-2 does not induce acute antidepressant effects in male or female mice, (2) PAM-2 induces antidepressant effects in mice from both sexes after one (subchronic) and two (chronic) weeks, whereas at the third week (chronic), the antidepressant effect is decreased in male and increased in female mice. Since PAM-2 does not influence the locomotor activity of mice, the observed antidepressant activity is not driven by nonspecific motor-stimulant actions, (3) the residual antidepressant effect mediated by PAM-2 after one week of treatment cessation is observed only in female mice, and finally the Ca2+ influx results indicate that (4) PAM-2 can reactivate desensitized α7 AChRs. Our results clearly indicate that PAM-2 elicits antidepressant activity, probably by enhancing the activity of the endogenous neurotransmitter acetylcholine on α7 AChRs, without inducing receptor desensitization, and that this activity is gender-dependent. This is the first time that an antidepressant activity is described for an α7 PAM, supporting further studies as potential therapeutic medications for depressive states.

The Vagus Nerve Attenuates Fulminant Hepatitis by Activating the Src Kinase in Kuppfer Cells

The parasympathetic nervous system has been known to modify innate immune responses. In animal models, acetylcholine (Ach) released from the distal ends of nerves has been shown to inhibit inflammatory responses such as endotoxic shock, pancreatitis, intestinal inflammation, etc. However, its role in LPS-induced fulminant hepatitis remains to be elucidated. Here, we demonstrate that the vagus nerve acts as a suppressor in the liver after challenge with LPS plus D-gal. The vagus nerve acts through the α7 AchR expressed on the surface of Kupffer cells, inhibiting the production of the proinflammatory cytokines TNF and IL-6. A mechanism study revealed that the suppressive effect of Ach may occur through the activation of Src kinase and subsequent inhibition of the Myd88 signal pathway. Our study has suggested a suppressive role of vagus nerve in the modulation of liver inflammatory responses, which should be noticed during clinical massive hepatectomy and liver transplantation. The nicotinic anti-inflammatory pathway may also be a potential target for sepsis after liver transplantation.

Acute Activation, Desensitization and Smoldering Activation of Human Acetylcholine Receptors

The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained “smoldering activation” occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β2)2β2 and (α4β2)2α4. The (α4β2)2β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β2)2α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

Differential Pharmacological Activity of JN403 between α7 and Muscle Nicotinic Acetylcholine Receptors

The differential action of the novel agonist JN403 at neuronal α7 and muscle nicotinic receptors (AChRs) was explored by using a combination of functional and structural approaches. Single-channel recordings reveal that JN403 is a potent agonist of α7 but a very low-efficacy agonist of muscle AChRs. JN403 elicits detectable openings of α7 and muscle AChRs at concentrations ~1000-fold lower and ~20-fold higher, respectively, than that for ACh. Single-channel activity elicited by JN403 is very similar to that elicited by ACh in α7 but profoundly different in muscle AChRs, where openings are brief and infrequent and do not appear in clusters at any concentration. JN403 elicits single-channel activity of muscle AChRs lacking the ε subunit, with opening events being more frequent and prolonged than those of wild-type AChRs. This finding is in line with the molecular docking studies predicting that JN403 may form a hydrogen bond required for potent activation at the α-δ but not at the α-ε binding site. JN403 does not elicit detectable Ca²⁺ influx in muscle AChRs but inhibits (±)-epibatidine-elicited influx mainly by a noncompetitive mechanism. Such inhibition is compatible with single-channel recordings revealing that JN403 produces open-channel blockade and early termination of ACh-elicited clusters, and it is therefore also a potent desensitizing enhancer of muscle AChRs. The latter mechanism is supported by the JN403-induced increase in the level of binding of [³H]cytisine and [³H]TCP to resting AChRs. Elucidation of the differences in activity of JN403 between neuronal α7 and muscle AChRs provides further insights into mechanisms underlying selectivity for α7 AChRs.

γ‐Aminobutyric acid type a receptor inhibition triggers a nicotinic neuroprotective mechanism

Nicotinic acetylcholine receptor (nAChR)-mediated neuroprotection has been implicated in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases and hypoxic ischemic events as well as other diseases hallmarked by excitotoxic and apoptotic neuronal death. Several modalities of nicotinic neuroprotection have been reported. However, although this process generally involves α4β2 and α7 subtypes, the underlying mechanisms are largely unknown. Interestingly, both activation and inhibition of α7 nAChRs have been reported to be neuroprotective. We have shown that inhibition of α7 nAChRs protects the function of acute hippocampal slices against excitotoxicity in an α4β2-dependent manner. Neuroprotection was assessed as the prevention of the N-methyl-D-aspartate-dependent loss of the area of population spikes (PSs) in the CA1 area of acute hippocampal slices. Our results support a model in which α7 AChRs control the release of γ-aminobutyric acid (GABA). Blocking either α7 or GABA(A) receptors reduces the inhibitory tone on cholinergic terminals, thereby promoting α4β2 activation, which in turn mediates neuroprotection. These results shed light on how α7 nAChR inhibition can be neuroprotective through a mechanism mediated by activation of α4β2 nAChRs.

Upregulation of the alpha7 nAChR in human macrophages is induced by chronic treatment with HIV‐1 envelope protein, gp120

Human immunodeficiency virus type‐1 (HIV‐1) infection is the commonest cause of dementia in adults less than 40 years. The cellular and molecular alterations that result in synaptic dysfunction, neuronal degeneration and cell death due to HIV‐associated dementia (HAD) by HIV‐1 infection appears to be caused by the infection of macrophages, microglia or by stem cells. We examined the effects of gp120 on the upregulation of the alpha7 nAChR expressed in human macrophages. Compared to controls, chronic treatment with gp120 showed a remarkable increase in the expression of the α7 nAChR with an increase in the concentration of gp120. In addition, macrophages chronically exposed to gp120 showed an increase the macroscopic whole‐cell currents compared to controls. After chronic exposure to gp120, macrophages also presented an increase in calcium uptake compared to non‐treated macrophages. Interestingly, experiments in several cell lines showed a similar up‐regulation of the α7 AChRs, suggesting that the up‐regulation could be occurring through a direct mechanism. We are currently conducting polysome analysis in continuous sucrose gradients to determine whether treatment with gp120 enhances the α7 nAChR mRNA association with the translational machinery. This notable up‐regulation of the α7 nAChR induced by the gp120 may be critical to the functional state of macrophages. Our data suggests that the α7 nAChR could be a key player in the HIV pathogenesis.This research work was supported by NIH GM008224, 2R01GM56371–11, NCRR 1S0RR13705 and by NIH SNRP‐U54NS4301 to JAL‐D. Also supported by NIH U54 Award CA96297–03 and NIH S06‐GM008102–3052. M.I.L is supported by RISE Award 2R25GM61151.

Cholinergic modulation of neurons in the gustatory region of the nucleus of the solitary tract

The rostral portion of the nucleus of the solitary tract (rNST) is an obligatory relay for gustatory afferent input on its way to the forebrain. Previous studies have demonstrated excitation of rNTS neurons by glutamate and substance P and inhibition by γ-aminobutyric acid (GABA) and met-enkephalin (ENK). Despite the existence of cholinergic neurons and putative terminals within the rNTS, there are no data on the effects of acetylcholine (ACh) on rNTS processing. Here, we use patch-clamp recording of rNTS neurons in vitro to examine ACh-mediated responses and voltage-gated conductances in these cells. Results revealed (1) intrinsic voltage-gated inhibition via activation of voltage-gated potassium A-channels ( I A), found almost exclusively in the medial rNTS, and hyperpolarization-activated potassium/sodium channels ( I h), found more frequently in the lateral rNST; and (2) ligand-gated inhibition via activation of muscarinic m2 ACh receptors (mAChRs) linked to inward rectifier potassium channels ( K ir) evenly distributed throughout the rNTS, a mechanism dependent on cholinergic inputs. Muscarinic responses were blocked by AFDX-116, a selective m2 mAChR antagonist, and by BaCl 2, an antagonist of K ir channels. In addition, many rNTS neurons exhibited excitation via α7 and non-α7 nicotinic AChRs. Non-α7 nAChRs, blocked by 10 μM mecamylamine, occurred more frequently in the lateral rNTS. In contrast, α7 nAChRs, blocked by 20 nM methyllcaconitine, were evenly distributed across the nucleus. As previously reported for voltage-activated conductances, none of these currents was related to neuronal morphology. These voltage- and ligand-dependent inhibitory mechanisms would be expected to contribute to the modulation of gustatory processing through the NST.

Antibodies against neuronal nicotinic receptor subtypes in neurological disorders

Patients with myasthenia gravis (MG) have antibodies to the muscle nicotinic acetylcholine receptor (mAChR) which are responsible for their muscle weakness: but some patients with MG and other neuroimmunological disorders have autonomic symptoms. We characterised the neuronal forms of AChRs (nAChRs) into two neuroblastoma cell lines and developed immunoprecipitation assays to test for antibodies to the α7- and α3-containing nAChR subtypes, present in the autonomic ganglia. We then tested 70 sera samples from MG patients, 38 from subjects with other neurological diseases, and 30 from healthy individuals, for antibodies to these two forms of neuronal AChR subtypes. We used the α7 subtype extracted from the human neuroblastoma IMR32 cell line labeled with 125 I -αBungarotoxin (αBgtx), and the α3-containing subtype extracted from the human neuroblastoma SY5Y cell line labeled with 3 H -Epibatidine (Epi). Nine subjects (five MG, one GBS, one CIPD and two LEMS) were positive for the α7 subtype; and four for the α3-containing subtype (two MG patients, one LEMS and the same GBS patient). None of the MG patients with undetectable levels of antibodies against muscle AChR were positive. The patients with serum antibodies to α7 or α3-containing neuronal AChRs showed a range of clinical features including autonomic symptoms and thymoma in two MG patients. These results indicate that patients with MG and other immune-mediated disorders can have antibodies to neuronal AChRs, and that these may contribute to the clinical characteristics of the diseases.

Alpha neurotoxins and their relatives: foes and friends?

Alpha neurotoxins and their relatives: foes and friends?