a(MESH:methyllycaconitine)

Entity

Name

methyllycaconitine

Namespace

MeSH

Namespace Version

20181007

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/01c9daa61012b37dd0a1bc962521ba51a15b38f1/external/mesh-names.belns

Curiously, although most studies are in agreement that nAChRs need to be activated to mediate their protective effects, mouse cortical neurons are protected by the alpha7 antagonist methyllycaconitine (Martin et al., 2004), raising the possibility that neuroprotection by alpha7 agonists may be through desensitization rather than activation of this rapidly desensitizing receptor. This would be consistent with the alpha7- dependent activation of intracellular signaling pathways by Abeta (Bell et al., 2004), but the opposite effects on cell survival exerted by Abeta and nicotine means that other mechanisms must be sought, such as ligand-specific coupling to downstream signaling pathways. PubMed:19293145

In support of this notion, beta-estradiol protects PC12 cells from amyloid toxicity, and this is prevented when alpha7 nAChRs are blocked with methyllycaconitine (Svensson and Nordberg, 1999). PubMed:19293145

Curiously, although most studies are in agreement that nAChRs need to be activated to mediate their protective effects, mouse cortical neurons are protected by the alpha7 antagonist methyllycaconitine (Martin et al., 2004), raising the possibility that neuroprotection by alpha7 agonists may be through desensitization rather than activation of this rapidly desensitizing receptor. This would be consistent with the alpha7- dependent activation of intracellular signaling pathways by Abeta (Bell et al., 2004), but the opposite effects on cell survival exerted by Abeta and nicotine means that other mechanisms must be sought, such as ligand-specific coupling to downstream signaling pathways. PubMed:19293145

In support of this notion, beta-estradiol protects PC12 cells from amyloid toxicity, and this is prevented when alpha7 nAChRs are blocked with methyllycaconitine (Svensson and Nordberg, 1999). PubMed:19293145

Notably, PHA could completely block the Ab-impaired task acquisition and reduce escape-latency to the normal level. Furthermore, the effect of PHA against the Ab-impaired task acquisition could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). It was also noted that blockade of a7 nAChR by MLA in the Gal-treated group resulted in a significant prolongation of the escape-latency on comparing with the Gal group (p<0.001) (Fig. 2). PubMed:25881725

MLA could completely block the PHA-induced spatial memory improvement (p<0.001). Furthermore, the effect of Gal against the Ab-impaired reference memory could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). However, a7 nAChR blockage in the Gal group has a lesser effect on reference memory in comparison of blockage of that receptor in the PHA group (p<0.05) (Fig. 4). PubMed:25881725

Inter-group analysis showed that the protein level decreased by pretreatment with selective a7 nAChR antagonist MLA (p<0.001). PHA and Gal prevent receptor destroying in AD animals, but this effect is completely abolished by MLA (p<0.001) (Fig. 9). The groups showed results in the cortex similar to those observed in the hippocampus (data not shown). PubMed:25881725

Notably, PHA could completely block the Ab-impaired task acquisition and reduce escape-latency to the normal level. Furthermore, the effect of PHA against the Ab-impaired task acquisition could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). It was also noted that blockade of a7 nAChR by MLA in the Gal-treated group resulted in a significant prolongation of the escape-latency on comparing with the Gal group (p<0.001) (Fig. 2). PubMed:25881725

MLA could completely block the PHA-induced spatial memory improvement (p<0.001). Furthermore, the effect of Gal against the Ab-impaired reference memory could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). However, a7 nAChR blockage in the Gal group has a lesser effect on reference memory in comparison of blockage of that receptor in the PHA group (p<0.05) (Fig. 4). PubMed:25881725

Inter-group analysis showed that the protein level decreased by pretreatment with selective a7 nAChR antagonist MLA (p<0.001). PHA and Gal prevent receptor destroying in AD animals, but this effect is completely abolished by MLA (p<0.001) (Fig. 9). The groups showed results in the cortex similar to those observed in the hippocampus (data not shown). PubMed:25881725

Notably, PHA could completely block the Ab-impaired task acquisition and reduce escape-latency to the normal level. Furthermore, the effect of PHA against the Ab-impaired task acquisition could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). It was also noted that blockade of a7 nAChR by MLA in the Gal-treated group resulted in a significant prolongation of the escape-latency on comparing with the Gal group (p<0.001) (Fig. 2). PubMed:25881725

Effect of a7 nAChRs blockage on time spent in target quadrant in probe trials. The implications of the a7 nAChRs on PHA- or Gal-induced spatial memory enhancement were investigated by pretreatment with normal saline or MLA. A two-way ANOVA revealed significant differences of treatment [F(1,56)=4.24, p<0.05], pretreatment [F(1,56)=96.87, p<0.001] and treatment  pretreatment interaction [F(1,32)=10.69, p<0.01]. Inter-group analysis showed that this effect was blocked by the selective a7 nAChR antagonist MLA (p<0.001). PubMed:25881725

Inter-group analysis showed that the protein level decreased by pretreatment with selective a7 nAChR antagonist MLA (p<0.001). PHA and Gal prevent receptor destroying in AD animals, but this effect is completely abolished by MLA (p<0.001) (Fig. 9). The groups showed results in the cortex similar to those observed in the hippocampus (data not shown). PubMed:25881725

MLA could completely block the PHA-induced spatial memory improvement (p<0.001). Furthermore, the effect of Gal against the Ab-impaired reference memory could be abolished by the pre-treatment of the a7 nAChR antagonist MLA (p<0.001). However, a7 nAChR blockage in the Gal group has a lesser effect on reference memory in comparison of blockage of that receptor in the PHA group (p<0.05) (Fig. 4). PubMed:25881725

Also, no alterations in the expression of a7 nAChR mRNA were observed in pretreatment with normal saline or MLA in PHA- or Gal-treated groups (p>0.05). In the same way, the pattern of mRNA expression in the cortex (data not shown) was similar to the hippocampus (Fig. 7). PubMed:25881725

The procognitive effect of MeM-3454 on episodic memory was completely blocked by the alpha7-specific antagonist methyllycaconitine, establishing that the efficacy of MeM-3454 can be attributed to alpha7 nAChR binding. PubMed:19721446