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Current Neuropharmacology 2016Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh... (Review)
Review
Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh from acetyl-CoA and choline in the cytoplasm and the vesicular acetylcholine transporter (VAChT) uptakes the neurotransmitter into synaptic vesicles. Following depolarization, ACh undergoes exocytosis reaching the synaptic cleft, where it can bind its receptors, including muscarinic and nicotinic receptors. ACh present at the synaptic cleft is promptly hydrolyzed by the enzyme acetylcholinesterase (AChE), forming acetate and choline, which is recycled into the presynaptic nerve terminal by the high-affinity choline transporter (CHT1). Cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer's disease (AD). AD is the most ordinary cause of dementia affecting 25 million people worldwide. The hallmarks of the disease are the accumulation of neurofibrillary tangles and amyloid plaques. However, there is no real correlation between levels of cortical plaques and AD-related cognitive impairment. Nevertheless, synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits. Thus, drugs that act on the cholinergic system represent a promising option to treat AD patients.
Topics: Acetylcholine; Alzheimer Disease; Animals; Cholinergic Agents; Cholinergic Neurons; Cholinesterase Inhibitors; Drug Delivery Systems; Humans; Receptors, Cholinergic
PubMed: 26813123
DOI: 10.2174/1570159x13666150716165726 -
Biomolecules Jun 2020It was a pleasure to receive a proposal to organize and be a guest editor of a Special Issue ofBiomolecules. This is the field in which I am working and personally know...
It was a pleasure to receive a proposal to organize and be a guest editor of a Special Issue ofBiomolecules. This is the field in which I am working and personally know some of the leadingscientists. My narrow field is the research on the peptide and protein neurotoxins from animalvenoms and their application as sophisticated tools for analysis of nicotinic acetylcholine receptors(nAChRs) [...].
Topics: Acetylcholine; Animals; Humans; Receptors, Cholinergic
PubMed: 32503306
DOI: 10.3390/biom10060852 -
Molecules (Basel, Switzerland) Mar 2022Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer's disease (AD), a... (Review)
Review
Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer's disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.
Topics: Acetylcholine; Alzheimer Disease; Cholinergic Agents; Humans; Neurodegenerative Diseases; Signal Transduction
PubMed: 35335180
DOI: 10.3390/molecules27061816 -
Neuropharmacology Jan 2016Neurons that produce acetylcholine (ACh) are positioned to broadly influence the brain, with axonal arborizations that extend throughout the cerebral cortex, striatum,... (Review)
Review
Neurons that produce acetylcholine (ACh) are positioned to broadly influence the brain, with axonal arborizations that extend throughout the cerebral cortex, striatum, and hippocampus. While the action of these neurons has typically been attributed entirely to ACh, neurons often release more than one primary neurotransmitter. Here, we review evidence for the cotransmission of the inhibitory neurotransmitter GABA from cholinergic neurons throughout the mammalian central nervous system. Functional cotransmission of ACh and GABA has been reported in the retina and cortex, and anatomical studies suggest that GABA cotransmission is a common feature of nearly all forebrain ACh-producing neurons. Further experiments are necessary to confirm the extent of GABA cotransmission from cholinergic neurons, and the contribution of GABA needs to be considered when studying the functional impact of activity in ACh-producing neurons. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.
Topics: Acetylcholine; Animals; Brain; Cholinergic Neurons; Humans; Mice; Optogenetics; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 26220313
DOI: 10.1016/j.neuropharm.2015.07.031 -
Current Opinion in Neurobiology Jun 2020Recent advances in neuroscience and immunology have shown that cholinergic signals are vital in the regulation of inflammation and immunity. Choline acetyltransferase... (Review)
Review
Recent advances in neuroscience and immunology have shown that cholinergic signals are vital in the regulation of inflammation and immunity. Choline acetyltransferase (ChAT) lymphocytes have the capacity to biosynthesize and release acetylcholine, the cognate ligand for cholinergic receptors. Acetylcholine-producing T cells relay neural signals in the 'inflammatory reflex' that regulate cytokine release in spleen. Mice deficient in acetylcholine-producing T cells have increased blood pressure, show reduced local vasodilatation and viral control in lymphocytic choriomeningitis virus infection, and display changes in gut microbiota compared with littermates. These observations indicate that ChAT lymphocytes play physiologically important roles in regulation of inflammation and anti-microbial defense. However, the full scope and importance of ChAT lymphocytes in immunity and vascular biology remains to be elucidated. Here, we review key findings in this emerging area.
Topics: Acetylcholine; Animals; Choline O-Acetyltransferase; Cytokines; Inflammation; Lymphocytes
PubMed: 32126362
DOI: 10.1016/j.conb.2020.01.017 -
Current Opinion in Neurobiology Oct 2016The olfactory bulb and piriform cortex are the best studied structures of the mammalian olfactory system and are heavily innervated by extrinsic neuromodulatory inputs.... (Review)
Review
The olfactory bulb and piriform cortex are the best studied structures of the mammalian olfactory system and are heavily innervated by extrinsic neuromodulatory inputs. The state-dependent release of acetylcholine, norepinephrine, serotonin, and other neuromodulators into these olfactory structures alters a constellation of physiological parameters in neurons and synapses that together modify the computations performed on sensory signals. These modifications affect the specificity, detectability, discriminability, and other properties of odor representations and thereby govern perceptual performance. Whereas different neuromodulators have distinct cellular effects, and tend to be associated with nominally different functions, it also is clear that these purported functions overlap substantially, and that ad hoc hypotheses regarding the roles of particular neuromodulators may have reached the limits of their usefulness.
Topics: Acetylcholine; Animals; Neurons; Olfactory Bulb; Smell
PubMed: 27564660
DOI: 10.1016/j.conb.2016.07.006 -
Chemico-biological Interactions Nov 2016The cholinergic system, comprising acetylcholine, the proteins responsible for acetylcholine synthesis and release, acetylcholine receptors and cholinesterases, is... (Review)
Review
The cholinergic system, comprising acetylcholine, the proteins responsible for acetylcholine synthesis and release, acetylcholine receptors and cholinesterases, is expressed by most human cell types. Acetylcholine is a neurotransmitter, but also a local signalling molecule which regulates basic cell functions, and cholinergic responses are involved in cell proliferation and apoptosis. So, activation of nicotinic and muscarinic receptors has a proliferative and anti-apoptotic effect in many cells. The content of choline acetyltransferase, acetylcholine receptors and cholinesterases is altered in many tumours, and cholinesterase content correlates with patient survival in some cancers. During apoptosis, acetylcholinesterase is induced and appears in the nuclei. Acetylcholinesterase participates in the regulation of cell proliferation and apoptosis through hydrolysis of acetylcholine and by other catalytic and non catalytic mechanisms, in a variant-specific manner. This review gathers information on the role of cholinergic system and specially acetylcholinesterase in cell proliferation and apoptosis.
Topics: Acetylcholine; Acetylcholinesterase; Apoptosis; Cell Proliferation; Choline O-Acetyltransferase; Humans; Neoplasms; Receptors, Muscarinic
PubMed: 27083142
DOI: 10.1016/j.cbi.2016.04.014 -
Nature Methods Sep 2018
Topics: Acetylcholine; Animals; Receptors, G-Protein-Coupled
PubMed: 30171237
DOI: 10.1038/s41592-018-0131-y -
Nature Communications Oct 2023Striatal dopamine encodes reward, with recent work showing that dopamine release occurs in spatiotemporal waves. However, the mechanism of dopamine waves is unknown....
Striatal dopamine encodes reward, with recent work showing that dopamine release occurs in spatiotemporal waves. However, the mechanism of dopamine waves is unknown. Here we report that acetylcholine release in mouse striatum also exhibits wave activity, and that the spatial scale of striatal dopamine release is extended by nicotinic acetylcholine receptors. Based on these findings, and on our demonstration that single cholinergic interneurons can induce dopamine release, we hypothesized that the local reciprocal interaction between cholinergic interneurons and dopamine axons suffices to drive endogenous traveling waves. We show that the morphological and physiological properties of cholinergic interneuron - dopamine axon interactions can be modeled as a reaction-diffusion system that gives rise to traveling waves. Analytically-tractable versions of the model show that the structure and the nature of propagation of acetylcholine and dopamine traveling waves depend on their coupling, and that traveling waves can give rise to empirically observed correlations between these signals. Thus, our study provides evidence for striatal acetylcholine waves in vivo, and proposes a testable theoretical framework that predicts that the observed dopamine and acetylcholine waves are strongly coupled phenomena.
Topics: Mice; Animals; Acetylcholine; Dopamine; Corpus Striatum; Neostriatum; Cholinergic Agents; Interneurons
PubMed: 37891198
DOI: 10.1038/s41467-023-42311-5 -
Current Pharmaceutical Design 2016Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because... (Review)
Review
Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review.
Topics: Acetylcholine; Animals; Cholinergic Agonists; Humans; Lung Neoplasms; Receptors, Muscarinic; Receptors, Nicotinic
PubMed: 26818857
DOI: 10.2174/1381612822666160127114237