Cross Talk Between Aluminum and Genetic Susceptibility and Epigenetic Modification in Alzheimer’s Disease

Liang, Ru‐Ping

doi:10.1007/978-981-13-1370-7_10

Cited by 13 publications

(4 citation statements)

References 111 publications

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“…Neurodegenerative diseases for years have been the subject of scientific interest from researchers worldwide due to the unclear mechanisms leading to their development. Recently, the neurotoxic effect of numerous environmental factors has been demonstrated [ 47 , 48 ]. One of them is exposure to aluminum and its compounds.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Neuroprotective Potential of Caffeinated Coffee in the Context of Aluminum-Induced Neurotoxicity: Insights from a PC12 Cell Culture Model

Rodak,

Bęben,

Birska

et al. 2024

Antioxidants

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Exposure to aluminum (Al) and its compounds is an environmental factor that induces neurotoxicity, partially through oxidative stress, potentially leading to the development of neurodegenerative diseases. Components of the diet, such as caffeinated coffee, may play a significant role in preventing these diseases. In the present study, an experimental model of PC12 cells (rat pheochromocytoma tumor cells) was developed to investigate the influence of caffeine and caffeinated coffee on neurotoxicity induced by Al compounds and/or oxidative stress. For the induction of neurotoxicity, aluminum maltolate (Almal) and H2O2 were used. The present study demonstrates that 100 μM Almal reduced cell survival, while caffeinated coffee with caffeine concentrations of 5 μg/mL and 80 μg/mL reversed this effect, resulting in a higher than fivefold increase in PC12 cell survival. However, despite the observed antioxidant properties typical for caffeine and caffeinated coffee, it is unlikely that they are the key factors contributing to cell protection against neurotoxicity induced by both oxidative stress and Al exposure. Moreover, the present study reveals that for coffee to exert its effects, it is possible that Al must first activate certain mechanisms within the cell. Therefore, various signaling pathways are discussed, and modifications of these pathways might significantly decrease the risk of Al-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Evaluating the Neuroprotective Potential of Caffeinated Coffee in the Context of Aluminum-Induced Neurotoxicity: Insights from a PC12 Cell Culture Model

Rodak,

Bęben,

Birska

et al. 2024

Antioxidants

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“…Aluminum has also been reported to induce the memory loss and neurological changes; experimentally, it has been proven that exposure to AlCl 3 can cause the neurological modifications which mimic the development and progression of neurodegeneration and ischemia in brain. 32 In this study, we found that exposure to AlCl 3 (50 mg/kg/day) may induce hemorrhage and reduce cellularity, degradation of neurons, and ischemia in the brain tissue; likewise, hemorrhage and ischemic neurons were also observed in the NaN 3 (17 mg/kg/day) treated group (Figures 6 and 7). The NaN 3 -induced neuronal oxidative stress has been shown to involve in the inhibition of cytochrome C oxidase which may interfere with numerous complexes in the electron transport chain, with the resultant ROS production.…”

Section: ■ Discussionmentioning

confidence: 99%

Comparative Biochemical Profiling of Aluminum Chloride and Sodium Azide Induced Neuroinflammation and Cardiometabolic Disturbance

et al. 2022

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Comorbidities in human beings signify the numerous risk factors that increase the incidences of neuro- and cardio-metabolic disorders. Experimental models depicting comorbidities are important to explore the molecular pathophysiology that can help suggest appropriate treatment strategies. Tissue-accumulating potential and pathological effects of aluminium chloride (AlCl3)and sodium azide (NaN3) are well recognized. Hence, in the current work, we have for the first time aimed to investigate the unexplored potential of graded dose effects of AlCl3 and NaN3 in inducing early inflammation and cardiometabolic toxicity via comparative biochemical analysis of AlCl3 and/or NaN3. Rats were allocated into seven groups (n = 6). Group 1 was normal control. Remaining groups were given graded doses of AlCl3 and/or NaN3, as LD-AlCl3 (AlCl3 40 mg), MD-AlCl3 (AlCl3 45 mg), and HD-AlCl3 (AlCl3 50 mg) representing low dose, medium dose, and high dose of AlCl3, respectively, and the remaining as LD-NaN3 (NaN3 13 mg), MD-NaN3 (NaN3 15 mg), and HD-NaN3 (NaN3 17 mg) representing low dose, medium dose, and high dose of NaN3, respectively. Serum levels of glucose, insulin, lipid profile, inflammatory mediators like IL-6 and oxidative stress marker, and malondialdehyde (MDA) were analyzed. Likewise, subacute toxicity parameters were analyzed. Immunohistochemistry (IHC) and histopathology (H&E/Masson’s trichrome staining) of brain, heart, and pancreatic tissues were done. ECG pattern of all groups was observed. HD-AlCl3 was associated with elevated levels of inflammatory biomarkers, MDA, and glycemic and lipid profiles, whereas it decreased the insulin levels. HD-NaN3 also showed the similar effects of aggravated inflammatory biomarkers, impaired glycemic and lipid profiles, but depicted the maximum mortality rate as compared to HD-AlCl3. IHC showed prominent amyloid plaques and neurofibrillary tangle formation with MD-AlCl3 and HD-AlCl3 as compared to NaN3-treated groups. Likewise, in brain tissues, vacuolation of white matter, vascular congestion, and hemorrhage were seen in HD-AlCl3 treated group, while HD-NaN3 induced death in animals. AlCl3 exposure resulted in an inverted QRS complex, while exposure to NaN3 showed ST depression but with increased mortality. AlCl3 has better controlled results as compared to NaN3 for induction of comorbid experimental animal model depicting early neuroinflammation and cardiometabolic disruption. These determined efforts facilitate the researchers for the development of clinically effective treatment strategies using such experimental models.

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“…Al has been found in senile plaques and NFTbearing neurons [74] and is particularly abundant in areas rich in cholinergic synapses [75]. It has a robust ability to induce epigenetic changes [76] due to its strong affinity for interaction with biological molecules, including DNA, RNA, and proteins [77].…”

Section: Ad Pathology Often Begins Several Yearsmentioning

confidence: 99%

Celecoxib effect on rivastigmine anti-Alzheimer activity against aluminum chloride-induced neurobehavioral deficits as a rat model of Alzheimer's disease; novel perspectives for an old drug

Abdel-Aal

Hussein

Elsaady

et al. 2021

Journal of Medical and Life Science

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Neuroinflammation plays a crucial role in Alzheimer's disease (AD) pathogenesis. Apoptosis, along with impaired neurogenesis, has been linked to AD neurodegenerative cell death, likely due to overexpression of cyclooxygenase-2 (COX-2). We investigated whether the concurrent administration of celecoxib, a selective COX-2 inhibitor, with rivastigmine, the standard anti-Alzheimer, would enhance rivastigmine anti-Alzheimer activity in the aluminum chloride (AlCl3) Alzheimer's rat model. Male rats were randomly assembled into control (Cont), AlCl3-treated (Al), rivastigmine-treated (RIVA), celecoxib-treated (Celeco), and combined rivastigmine and celecoxib-treated (RIVA+Celeco) groups. They were studied for memory, and cognitive skills, along with evaluating hippocampal acetylcholinesterase (AChE) activity. Hippocampal neuropathology, besides apoptosis, astroglial injury, and neurogenesis, were assessed through examining the expression of their related protein markers; activated caspase-3, glial fibrillary acidic protein (GFAP), and nestin. Celecoxib, rivastigmine, and their combination attenuated AlCl3induced intellectual impairment and the associated neurodegenerative changes. However, the combination therapy had no additional neuroprotective advantage over rivastigmine alone, except for the enhancement of neurogenesis and suppression of apoptosis in the AL-intoxicated rats. As compared to rivastigmine, the efficacy of celecoxib in combination with rivastigmine confers neuroprotection only at the cellular level, enhancement of neurogenesis, and suppression of apoptosis, without having a mitigating effect on Al-induced cognitive impairment.

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Cross Talk Between Aluminum and Genetic Susceptibility and Epigenetic Modification in Alzheimer’s Disease

Cited by 13 publications

References 111 publications

Evaluating the Neuroprotective Potential of Caffeinated Coffee in the Context of Aluminum-Induced Neurotoxicity: Insights from a PC12 Cell Culture Model

Evaluating the Neuroprotective Potential of Caffeinated Coffee in the Context of Aluminum-Induced Neurotoxicity: Insights from a PC12 Cell Culture Model

Comparative Biochemical Profiling of Aluminum Chloride and Sodium Azide Induced Neuroinflammation and Cardiometabolic Disturbance

Celecoxib effect on rivastigmine anti-Alzheimer activity against aluminum chloride-induced neurobehavioral deficits as a rat model of Alzheimer's disease; novel perspectives for an old drug

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