p(FPLX:CHRM)
Although Aβ peptides negatively alter the cholinergic system at multiple sites, including ACh synthesis, ACh release, and muscarinic receptors (157), the discovery that Aβ1−42 binds to α7 nAChRs with high affinity suggested the potential for a causal role of nAChRs in AD (159, 160). PubMed:17009926
When cholinergic neurons are depolarized, ACh is exocytosed from synaptic vesicles and released into the synaptic cleft, where it can activate both muscarinic and nicotinic receptors PubMed:26813123
The two best known muscarinic receptor antagonists are atropine and quinuclidinyl benzilate, which block all muscarinic receptors PubMed:26813123
The two best known muscarinic receptor antagonists are atropine and quinuclidinyl benzilate, which block all muscarinic receptors PubMed:26813123
The first selective agonist identified for muscarinic receptors was muscarine and, so far, there is no agonist available with a specific selectivity for one particular subtype of muscarinic receptor PubMed:26813123
In addition, quantitative autoradiography assay revealed that choline uptake was reduced in the hippocampus of these animals and that the expression of muscarinic and nicotinic cholinergic receptors was diminished PubMed:26813123
Binding studies performed with the use of [3H]-nicotine and [3H]-ACh showed a significant reduction in nicotine and ACh binding sites in cerebral cortex of patients suffering from AD, demonstrating a decrease of both nAChR and mAChR populations (Gotti et al., 2006a; Paterson and Nordberg, 2000; Perry et al., 1981, 1985, 1987, 1988; Shimohama et al., 1986; Whitehouse et al., 1981, 1982, 1986) PubMed:25514383
We now realize that acetylcholine liberated from cholinergic nerve terminals often activates both nAChRs and muscarinic receptors PubMed:21482353
Muscarinic receptors are G protein coupled receptors that are capable of modulating a wide variety of ion channels PubMed:26813123
As a consequence, stimulation of ACh muscarinic receptors can promote the opening or closing of Ca2+, K+, or Cl- channels, which might facilitate either depolarization or hyperpolarization, depending on the cell type where these receptors are expressed PubMed:26813123
As a consequence, stimulation of ACh muscarinic receptors can promote the opening or closing of Ca2+, K+, or Cl- channels, which might facilitate either depolarization or hyperpolarization, depending on the cell type where these receptors are expressed PubMed:26813123
Activation of muscarinic receptors can block various types of K+ currents by inhibiting many resting and voltage-gated K+ channels PubMed:26813123
As a consequence, stimulation of ACh muscarinic receptors can promote the opening or closing of Ca2+, K+, or Cl- channels, which might facilitate either depolarization or hyperpolarization, depending on the cell type where these receptors are expressed PubMed:26813123
In addition to decreasing K+ currents, muscarinic receptors located at the presynaptic region can also inhibit GABAergic neurotransmission PubMed:26813123
The neurotransmitter ACh binds to two families of receptors, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs). Both families of receptors regulate the cognitive processes mentioned above (Ghoneim and Mewaldt, 1977; Petersen, 1977; Sarter and Paolone, 2011), and are both affected in AD PubMed:25514383
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.