α7-Nicotinic Acetylcholine Receptors: New Therapeutic Avenues in Alzheimer’s Disease

Öz, Murat; Petroianu, Georg; Lorke, Dietrich

doi:10.1007/978-1-4939-3768-4_9

Cited by 10 publications

(5 citation statements)

References 127 publications

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“…Multiple evidence suggests the involvement of brain α7 nAChRs in the development and progression of AD (reviewed in refs. [31,52,53]). However, the time course of α7 dysfunction during AD development and the underlying molecular mechanisms are not completely understood.…”

Section: Discussionmentioning

confidence: 99%

Impairment of brain function in a mouse model of Alzheimer’s disease during the pre-depositing phase: the role of α7 nicotinic acetylcholine receptors

Lykhmus,

Tzeng,

Koval

et al. 2024

Preprint

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Alzheimer’s disease (AD) is an age-dependent incurable neurodegenerative disorder accompanied by neuroinflammation, amyloid accumulation and memory impairment. It begins decades before the first clinical symptoms appear, and identifying early biomarkers is key for developing disease-modifying therapies. We show now in a mouse model of AD that before any amyloid deposition the brains of 1.5-month-old mice contain increased levels of pro-inflammatory cytokines IL-1β and IL-6, decreased levels of nicotinic acetylcholine receptors (nAChRs) in the brain and brain mitochondria and increased amounts of α7 nAChR-bound Aβ1-42, along with impaired episodic memory and increased risk of apoptosis. Both acute (1-week-long) and chronic (4-month-long) treatments with α7-selective agonist PNU282987, starting at 1.5 months of age, were well tolerated. The acute treatment did not affect the levels of soluble Aβ1-42but consistently upregulated the α7 nAChR expression, decreased the level of α7- Aβ1-42complexes and improved episodic memory of 1.5-month-old mice. The chronic treatment, covering the disease development phase, strongly upregulated the expression of all abundant brain nAChRs, reduced both free and α7-coupled Aβ1-42within the brain, had anti-inflammatory and antiapoptotic effects, and potently upregulated cognition, thus identifying α7 nAChRs as both early biomarker and potent therapeutic target for fighting this devastating disease.

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Section: Discussionmentioning

confidence: 99%

Impairment of brain function in a mouse model of Alzheimer’s disease during the pre-depositing phase: the role of α7 nicotinic acetylcholine receptors

Lykhmus,

Tzeng,

Koval

et al. 2024

Preprint

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“…CHE is an important enzyme involved in acetyl choline catabolism at cholinergic synapses into acetic acid and choline [55]. Also, CHE is considered a target enzyme for Cis induced cerebral damage as the inhibition of CHE activity leads to the disturbance of the neurotransmitter acetylcholine [56] and an obvious disturbance in the nerve impulse transmission will take place [57].…”

Section: Discussionmentioning

confidence: 99%

Ginkgo biloba Alleviates Cisplatin-Mediated Neurotoxicity in Rats via Modulating APP/Aβ/P2X7R/P2Y12R and XIAP/BDNF-Dependent Caspase-3 Apoptotic Pathway

et al. 2020

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Neurotoxicity is an obvious adverse effect in Patients encountering a complete course of chemotherapy. The present work is conducted to evaluate the neuroprotective effect of Ginkgo biloba (Ginkgo) against the neurotoxicity induced by Cisplatin (Cis) in rats. Forty male Wistar albino rats were arranged into four groups: (1) Control group, rats were given saline; (2) Cis group, rats were injected by Cis 2 mg/kg body weight i.p., twice a week starting on the fifth day for thirty days; (3) Ginkgo group, rats were administered Ginkgo (50 mg/kg orally) daily for thirty days; and (4) Ginkgo+Cis group, rats received Ginkgo (50 mg/kg orally) daily and on the fifth day, rats were injected with Cis (2 mg/Kg body weight i.p.) twice a week for thirty days. Cis significantly increased Gamma glutamyltransferase (GGT) and Acetyl Cholinesterase (CHE) as compared to the control group and also disturbed cerebral oxidative/antioxidant redox. Co-administration of Ginkgo and Cis reversed the adverse effect of Cis on the brain tissue. Moreover, co-administration of Ginkgo and Cis ameliorated Cis induced brain damage by reducing Amyloid precursor protein (APP), amyloid β (Aβ), P2Y12R and P2X7R mRNA expressions and proteins. Furthermore, Ginkgo regulated XIAP/BDNF expressions with a consequent decrease of caspase-3 and DNA fragmentation%. The current results concluded that concurrent treatment with Ginkgo can mitigate neurotoxicity mediated by Cis in experimental animals through exhibiting antioxidant effect by restoring cerebral oxidative/antioxidant redox and anti-apoptotic effect via regulating cerebral APP/Aβ/P2Y12R/P2X7R and XIAP/BDNF signaling pathways.

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“…Potentiation of cholinergic signalling by nicotine and other nAChR agonists has been implicated in the treatment of various neurodegenerative and non-neurodegenerative disorders that primarily or secondarily affect this system (Mufson et al, 2008;Quik et al, 2008;Liepelt et al, 2010;Oz et al, 2016). Thus, it seems that the cholinergic properties of nicotine may favour its use in the treatment of agerelated cognitive deficits and memory loss.…”

Section: Cholinergic Degenerationmentioning

confidence: 99%

Revisiting nicotine’s role in the ageing brain and cognitive impairment

Majdi

Kamari

Vafaee

et al. 2017

Reviews in the Neurosciences

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AbstractBrain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative stress, excitotoxicity, amyloid-β toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening in age-related changes in diverse molecular pathways leading to pathology. Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors. Additionally, nicotine administration should result in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment.

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α7-Nicotinic Acetylcholine Receptors: New Therapeutic Avenues in Alzheimer’s Disease

Cited by 10 publications

References 127 publications

Impairment of brain function in a mouse model of Alzheimer’s disease during the pre-depositing phase: the role of α7 nicotinic acetylcholine receptors

Impairment of brain function in a mouse model of Alzheimer’s disease during the pre-depositing phase: the role of α7 nicotinic acetylcholine receptors

Ginkgo biloba Alleviates Cisplatin-Mediated Neurotoxicity in Rats via Modulating APP/Aβ/P2X7R/P2Y12R and XIAP/BDNF-Dependent Caspase-3 Apoptotic Pathway

Revisiting nicotine’s role in the ageing brain and cognitive impairment

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