Alpha 7 nicotinic acetylcholine receptor and its effects on Alzheimer's disease

Ma, Kai; Qian, Yi‐Hua

doi:10.1016/j.npep.2018.12.003

Cited by 109 publications

(89 citation statements)

References 95 publications

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“…Up-regulation of α7nAChR is a therapeutic goal in AD and schizophrenia since it can form complexes with Aβ slowing down amyloid plaque deposition, thus prevents Aβ-induced cytotoxicity. New evidence indicates that intracellular Aβ accumulates in α7nAChR positive neurons [ 19 , 20 ]. Other observations confirm a significant decrease in M1mAChR and M4mAChR during various stages of AD [ 21 ].…”

Section: Cholinergic Signaling and Polyphenolsmentioning

confidence: 99%

Neuroprotective Polyphenols: A Modulatory Action on Neurotransmitter Pathways

Rębas

Rzajew

Radzik

et al. 2020

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Background: Balance in neurotransmission is essential for the proper functioning of the nervous system and even a small, but prolonged disturbance, can induce the negative feedback mechanisms leading to various neuropathologies. Neurodegenerative and mood disorders such as Alzheimer’s, Parkinson’s or affective disorders are increasing medical and social problems. Among the wide spectrum of potentially destructive events, oxidative stress and disrupted metabolism of some neurotransmitters such as acetylcholine, GABA, glutamate, serotonin or dopamine appear to play a decisive role. Biologically active plant polyphenols have been shown to exert a positive impact on the function of the central nervous system by modulation of metabolism and the action of some neurotransmitters. Methods: Based on published research, the pharmacological activities of some naturally occurring polyphenols have been reviewed, with a focus on their potential therapeutic importance in the regulation of neurotransmitter systems. Results: Phytochemicals can be classified into several groups and most of them possess anticancer, antioxidative, anti-inflammatory and neuroprotective properties. They can also modulate the metabolism or action of some neurotransmitters and/or their receptors. Based on these properties, phytochemicals have been used in traditional medicine for ages, although it was focused mainly on treating symptoms. However, growing evidence indicates that polyphenols may also prevent or slow neurological diseases. Conclusion: Phytochemicals seem to be less toxic than synthetic drugs and they can be a safer alternative for currently used preparations, which exert adverse side effects. The neuroprotective actions of some plant polyphenols in the regulation of neurotransmitters metabolism, functioning of neurotransmitters receptors and antioxidative defense have potential therapeutic applications in various neurodegenerative disorders.

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Section: Cholinergic Signaling and Polyphenolsmentioning

confidence: 99%

Neuroprotective Polyphenols: A Modulatory Action on Neurotransmitter Pathways

Rębas

Rzajew

Radzik

et al. 2020

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“…The homomeric α7 subtype plays a crucial role in various cognitive functions, including learning and memory [ 4 , 5 ]. There is also substantial experimental evidence supporting the notion that α7 nAChRs are critically involved in the pathogenesis of Alzheimer disease (AD) [ 6 , 7 , 8 ]. They colocalize with amyloid plaques [ 9 ], and the amyloid β peptide (Aβ) binds to α7 nAChRs [ 9 ], probably leading to internalization of Aβ by endocytosis with the ensuing build-up of intracellular Aβ [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…They colocalize with amyloid plaques [ 9 ], and the amyloid β peptide (Aβ) binds to α7 nAChRs [ 9 ], probably leading to internalization of Aβ by endocytosis with the ensuing build-up of intracellular Aβ [ 10 , 11 ]. α7 nAChR-expressing neurons are the most susceptible to AD neuropathology; both α7 nAChR binding sites and α7 nAChR protein levels are reduced in the brains of AD patients [ 6 ], influencing the neuroinflammation associated with AD [ 6 ]. Currently, it is not clear whether downregulation or upregulation of α7 nAChRs is related to the pathogenesis of AD.…”

Section: Introductionmentioning

confidence: 99%

Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons

et al. 2020

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Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01–1 µM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 nAChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein receptor levels as determined by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 µM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium.

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“…Single nucleotide polymorphisms resulting in overexpression of a dominant negative version of the CHRNA7 gene (CHRNA7A) as well as reduced expression of α7 nAChRs have been found in the brains of schizophrenic patients (Stevens et al 2014; Kunii et al 2015). Furthermore, positive allosteric modulators of α7 nAChRs have been investigated as a potential treatment for a variety of disorders, including Alzheimer’s disease in which the cholinergic system diminishes (Bertrand et al 2015; Dineley et al 2015; Ma and Qian 2019). Thus, understanding the processes of α7 nAChRs signaling in the hippocampus is critical to understanding normal brain function and developing treatments for neuropsychiatric and neurodegenerative disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Both α7 nAChR-mediated cholinergic signaling and hippocampal neurogenesis have been shown to play important roles in learning and memory processes. Cholinergic signaling supports synaptic plasticity in a timing-dependent manner (Gu and Yakel 2011; Haam and Yakel 2017) and positive allosteric modulators of α7 nAChR have been heavily investigated for their ability to promote cognitive function (Ma and Qian 2019). Ongoing hippocampal neurogenesis plays an important, though hotly debated, role in learning and memory processes (Shors et al 2002; Nakashiba et al 2012; Vicidomini et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Loss of α7 nicotinic acetylcholine receptors in GABAergic interneurons causes sex-dependent impairments in postnatal neurogenesis and cognitive and social behavior

Otto²,

Ac³

et al. 2020

Preprint

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Neural stem cells within the subgranular zone of the dentate gyrus (DG) generate new neurons that form the granule cell layer during embryonic development and continue to generate new neurons throughout life. The maturation process of newly generated granule cells is modulated by nicotinic acetylcholine receptors (nAChRs), which have been shown to play a role in cell survival, signal modulation, dendritic integration, and memory formation. Disrupted nAChR signaling has been implicated in neuropsychiatric and neurodegenerative disorders, potentially via alterations in DG neurogenesis. GABAergic interneurons are known to express nAChRs, particularly the α7 subunit, and have been shown to shape development, integration, and circuit reorganization of DG granule cells. Therefore, we examined the effects of conditional deletion of α7 nAChRs in GABAergic interneurons on measures of postnatal neurogenesis and behavioral outcomes. Loss of α7 nAChRs resulted in a decrease of postnatal granule cells, as indicated by reduced GFAP+ cells in the DG, specifically in male mice, as well as sex-dependent changes in several behaviors, including social recognition, object investigation, and spatial learning. Overall, these findings suggest α7 nAChRs expressed in GABAergic interneurons play an important role in regulating postnatal neurogenesis and behavior in a sex-dependent manner. This provides important insight into the mechanisms by which cholinergic dysfunction contributes to the cognitive and behavioral changes associated with neurodevelopmental and neurodegenerative disorders.

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Alpha 7 nicotinic acetylcholine receptor and its effects on Alzheimer's disease

Cited by 109 publications

References 95 publications

Neuroprotective Polyphenols: A Modulatory Action on Neurotransmitter Pathways

Neuroprotective Polyphenols: A Modulatory Action on Neurotransmitter Pathways

Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons

Loss of α7 nicotinic acetylcholine receptors in GABAergic interneurons causes sex-dependent impairments in postnatal neurogenesis and cognitive and social behavior

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