Amyloid-β production in aged guinea pigs: atropine-induced enhancement is reversed by naloxone

Ionov, Ilya D.; Pushinskaya, Irina I.

doi:10.1016/j.neulet.2010.06.010

Cited by 8 publications

(7 citation statements)

References 36 publications

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“…15 Moreover, in animal models, reduced cholinergic transmission via atropine or cortical cholinergic denervation increased amyloid beta concentrations. 38-40 …”

Section: Discussionmentioning

confidence: 99%

Cumulative Use of Strong Anticholinergics and Incident Dementia

et al. 2015

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“…15 Moreover, in animal models, reduced cholinergic transmission via atropine or cortical cholinergic denervation increased amyloid beta concentrations. 38-40 …”

Section: Discussionmentioning

confidence: 99%

Cumulative Use of Strong Anticholinergics and Incident Dementia

et al. 2015

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“…This process could result from an interlink between the cholinergic pathway and amyloidogenesis. 35,37 Furthermore, the reduced release of acetylcholine inflicted by Aβ and vice versa was observed. 38 4.3.…”

Section: Chemically Induced Intraperitoneal Administrationmentioning

confidence: 92%

Preclinical Models for Alzheimer’s Disease: Past, Present, and Future Approaches

et al. 2022

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A robust preclinical disease model is a primary requirement to understand the underlying mechanisms, signaling pathways, and drug screening for human diseases. Although various preclinical models are available for several diseases, clinical models for Alzheimer’s disease (AD) remain underdeveloped and inaccurate. The pathophysiology of AD mainly includes the presence of amyloid plaques and neurofibrillary tangles (NFT). Furthermore, neuroinflammation and free radical generation also contribute to AD. Currently, there is a wide gap in scientific approaches to preventing AD progression. Most of the available drugs are limited to symptomatic relief and improve deteriorating cognitive functions. To mimic the pathogenesis of human AD, animal models like 3XTg-AD and 5XFAD are the primarily used mice models in AD therapeutics. Animal models for AD include intracerebroventricular-streptozotocin (ICV-STZ), amyloid beta-induced, colchicine-induced, etc., focusing on parameters such as cognitive decline and dementia. Unfortunately, the translational rate of the potential drug candidates in clinical trials is poor due to limitations in imitating human AD pathology in animal models. Therefore, the available preclinical models possess a gap in AD modeling. This paper presents an outline that critically assesses the applicability and limitations of the current approaches in disease modeling for AD. Also, we attempted to provide key suggestions for the best-fit model to evaluate potential therapies, which might improve therapy translation from preclinical studies to patients with AD.

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“…The key role of cholinergic tone is confirmed by animal experiments in which basal forebrain lesions (an animal model of AD) or by treatment with anticholinergics (blocking acetylcholine receptors) triggers the formation of β-amyloid in transgenic mice [34,35], rats [36], guinea pigs [37], and rabbits [38]. These animal models suggest that all or most normal (non-transgenic) mammalian brains have an incipient age-related capacity to produce amyloid like that which occurs spontaneously in aged primates [39].…”

Section: Ache Inhibitors and Anticholinergics Affect Neurodegeneratiomentioning

confidence: 92%

“…These animal models suggest that all or most normal (non-transgenic) mammalian brains have an incipient age-related capacity to produce amyloid like that which occurs spontaneously in aged primates [39]. Furthermore, the extent of amyloid production occurs on a continuum that is substantially skewed upward toward older animals, those with basal forebrain cholinergic lesions, and those with transgenic with human amyloid-related genes [34][35][36][37][38][39]. The importance of AChE inhibitors, which restore cholinergic function by amplifying the effect of synaptic acetylcholine, is shown by the fact that they are prophylactic against some of these changes [38,40].…”

Section: Ache Inhibitors and Anticholinergics Affect Neurodegeneratiomentioning

confidence: 99%

Improving Anti-Neurodegenerative Benefits of Acetylcholinesterase Inhibitors in Alzheimer’s Disease: Are Irreversible Inhibitors the Future?

Moss

2020

IJMS

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Decades of research have produced no effective method to prevent, delay the onset, or slow the progression of Alzheimer’s disease (AD). In contrast to these failures, acetylcholinesterase (AChE, EC 3.1.1.7) inhibitors slow the clinical progression of the disease and randomized, placebo-controlled trials in prodromal and mild to moderate AD patients have shown AChE inhibitor anti-neurodegenerative benefits in the cortex, hippocampus, and basal forebrain. CNS neurodegeneration and atrophy are now recognized as biomarkers of AD according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) criteria and recent evidence shows that these markers are among the earliest signs of prodromal AD, before the appearance of amyloid. The current AChE inhibitors (donepezil, rivastigmine, and galantamine) have short-acting mechanisms of action that result in dose-limiting toxicity and inadequate efficacy. Irreversible AChE inhibitors, with a long-acting mechanism of action, are inherently CNS selective and can more than double CNS AChE inhibition possible with short-acting inhibitors. Irreversible AChE inhibitors open the door to high-level CNS AChE inhibition and improved anti-neurodegenerative benefits that may be an important part of future treatments to more effectively prevent, delay the onset, or slow the progression of AD.

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Amyloid-β production in aged guinea pigs: atropine-induced enhancement is reversed by naloxone

Cited by 8 publications

References 36 publications

Cumulative Use of Strong Anticholinergics and Incident Dementia

Cumulative Use of Strong Anticholinergics and Incident Dementia

Preclinical Models for Alzheimer’s Disease: Past, Present, and Future Approaches

Improving Anti-Neurodegenerative Benefits of Acetylcholinesterase Inhibitors in Alzheimer’s Disease: Are Irreversible Inhibitors the Future?

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