Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment

Lombardo, Sylvia; Maskos, Uwe

doi:10.1016/j.neuropharm.2014.11.018

Cited by 252 publications

(156 citation statements)

References 111 publications

(146 reference statements)

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“…Incidentally, the up-regulation of mGluR5 has been also found in plaque-surrounding cortical astrocytes associated with senile plaques in the APPswe/PS1dE9 mouse model, as well as in post-mortem human tissues [112,113]. As alluded to earlier, α7 nicotinic cholinoreceptor (α7nAChR) binds β -amyloid with high affinity and can be modulated by ιτ is [126]. Chronic treatment with low β-amyloid concentrations (0.1 -100 nM), however, up-regulates several cholinoreceptors including those containing α7, α4 and β2 subunits [127].…”

Section: Effects Of β-Amyloidmentioning

confidence: 90%

Astroglial calcium signalling in Alzheimer's disease

Verkhratsky

Rodriguez-Arellano

Parpura

et al. 2017

Biochemical and Biophysical Research Communications

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Neuroglial contribution to Alzheimer's disease (AD) is pathologically relevant and highly heterogeneous. Reactive astrogliosis and activation of microglia contribute to neuroinflammation, whereas astroglial and oligodendroglial atrophy affect synaptic transmission and underlie the overall disruption of the central nervous system (CNS) connectome. Astroglial function is tightly integrated with the intracellular ionic signalling mediated by complex dynamics of cytosolic concentrations of free Ca 2+ and Na + . Astroglial ionic signalling is mediated by plasmalemmal ion channels, mainly associated with ionotropic receptors, pumps and solute carrier transporters, and by intracellular organelles comprised of the endoplasmic reticulum and mitochondria. The relative contribution of these molecular cascades/organelles can be plastically remodelled in development and under environmental stress. In AD astroglial Ca 2+ signalling undergoes substantial reorganisation due to an abnormal regulation of expression of Ca 2+ handling molecular cascades.

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Section: Effects Of β-Amyloidmentioning

confidence: 90%

Astroglial calcium signalling in Alzheimer's disease

Verkhratsky

Rodriguez-Arellano

Parpura

et al. 2017

Biochemical and Biophysical Research Communications

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“…Thus, there are putative benefits and disadvantages to agonism and antagonism of this receptor that are dependent on the prevailing physiological conditions; both antagonists and agonists can have benefit but also exhibit biphasic effects [207,208]. At this juncture, it is therefore unclear whether or not this is an important target for CBD.…”

Section: Cbd Receptor Targets In Neurodegenerationmentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

462

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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“…Several brain areas are affected including the hippocampus, temporal lobe, and frontal cortex. Particularly, the cholinergic innervation is severely disrupted [50]. The exact cause of the disease remains contentious.…”

Section: Iron In Alzheimer's Diseasementioning

confidence: 99%

Iron, Aging, and Neurodegeneration

Angelova

Brown

2015

Metals

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Abstract:Iron is a trace element of considerable interest to both chemistry and biology. In a biological context its chemistry is vital to the roles it performs. However, that same chemistry can contribute to a more deleterious role in a variety of diseases. The brain is a very sensitive organ due to the irreplaceable nature of neurons. In this regard regulation of brain iron chemistry is essential to maintaining neuronal viability. During the course of normal aging, the brain changes the way it deals with iron and this can contribute to its susceptibility to disease. Additionally, many of the known neurodegenerative diseases have been shown to be influenced by changes in brain iron. This review examines the role of iron in the brain and neurodegenerative diseases and the potential role of changes in brain iron caused by aging.

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Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment

Cited by 252 publications

References 111 publications

Astroglial calcium signalling in Alzheimer's disease

Astroglial calcium signalling in Alzheimer's disease

Molecular Targets of Cannabidiol in Neurological Disorders

Iron, Aging, and Neurodegeneration

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