Aluminum neurotoxicity and autophagy: a mechanistic view

Makhdoomi, Sajjad; Ariafar, Saba; Mirzaei, Fatemeh; Mohammadi, Mojdeh

doi:10.1080/01616412.2022.2132727

Cited by 14 publications

(5 citation statements)

References 120 publications

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“…Air, water and different types of food, especially preserved food or food with additives, are sources of Al [27]. It is well documented that Al is a neurotoxic metal [28] and there are important studies such as Islam et al (1999) [29] who described the neurodegenerative disorder known as motor neuron disease among 17-30 year olds due to prolonged Al exposure [29]. Also, kidney patients undergoing dialysis treatment are exposed to high concentrations of Al, which lead to neurotoxicity and bone disease [30].…”

Section: Discussionmentioning

confidence: 99%

Aluminum Concentrations in Male and Female Football Players during the Season

Robles-Gil,

Toro-Román,

Maynar-Mariño

et al. 2023

Toxics

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Aluminum (Al) is one of the most abundant trace mineral elements in the earth’s crust. Al is considered a potent neurotoxicant. Physical exercise could cause modifications in some trace mineral elements. On the other hand, there could be sex differences in the exposure and deposits of toxic mineral elements. The aim of the present study was to compare sex and seasonal differences in extracellular and intracellular Al concentrations in football players. The study involved 22 male and 24 female football players from the fifth and second national category, respectively. Three assessments were carried out during the season (beginning, middle and end). Al concentrations in plasma, urine, erythrocytes and platelets were determined. Male football players ingested more Al (p < 0.05). Higher plasma Al concentrations were reported in male football players (p < 0.01). On the other hand, in both groups, increases and decreases in Al in the plasma and urine were observed in the second and third assessment, respectively (p < 0.01). There were sex differences in platelet Al concentrations (p < 0.05). Plasma and platelet Al concentrations may be different between the sexes. Al concentrations may change over the course of a season in football players.

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Section: Discussionmentioning

confidence: 99%

Aluminum Concentrations in Male and Female Football Players during the Season

Robles-Gil,

Toro-Román,

Maynar-Mariño

et al. 2023

Toxics

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“…This collective mélange of perturbations constitutes a significant facet of Aβ pathology. On a distinct metal note, aluminum emerges as a pathological instigator in the pathogenesis of AD, imparting neurotoxicity and substantiating influence upon Aβ genesis [46]. Preliminary investigations elucidate the propensity of aluminum ions to potentiate the aggregation of physiological Aβ concentrations in vitro [47].…”

Section: The Role Of Metal Ions In Admentioning

confidence: 99%

Deciphering the Significance of Metal Ions in the Pathogenesis of Alzheimer's Disease and Forging Pathways Towards Prospective Therapeutic Strategies

JunYi,

Wang,

Liu

et al. 2023

Preprint

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Alzheimer’s disease (AD), a neurodegenerative condition, is characterized by its progressive cognitive decline, which includes memory impairment, language alterations, visuospatial challenges, and compromised executive functions. The primary pathological features of AD involve the formation of extracellular senile plaques primarily composed of β-amyloid (Aβ) and the accumulation of hyperphosphorylated tau proteins, leading to the creation of neurofibrillary tangles. With an aging global population and a lack of effective AD treatments, there is an urgent need for comprehensive AD research. Metallic elements like iron, zinc, copper, and manganese play essential roles in human development, metabolic pathways, and brain maturation. Accumulating evidence suggests that these metal ions significantly influence the development of AD, contributing to processes such as Aβ deposition, oxidative stress, neuroinflammatory responses, and disruptions in autophagy and apoptosis, among other cascading effects. Therefore, a thorough investigation into the relationship between metals and AD is crucial, not only to identify new pre-pathogenic interventions targeting metal ions but also to support the development of tailored AD treatments. This manuscript extensively explores the connection between metallic elements, specifically copper, iron, zinc, and manganese, in physiological processes and their intricate relationship with AD. It emphasizes the importance of understanding the regulation of the metal ion signaling network throughout the AD continuum to offer new perspectives and potential approaches for developing innovative metal ion modulators to combat AD. This research holds promise for addressing the global challenge of AD.

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“…Autophagy dysfunction is involved in the pathogenesis of neurodegenerative disorders. Intriguingly, it was observed that the expression of autophagy-associated proteins, such as autophagy-related genes 5 (Atg5), Beclin-1, and LC3II, was intensely declined in the aluminum chloride-treated rats, while downregulated autophagy process resulted in reduced autophagic clearance of Aβ protein aggregates [8]. Taken together, The pathological mechanism of cognitive impairment induced by Al is closely related to oxidative stress and autophagy dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…So Al-induced AD model is an excellent model for screening new anti-AD drugs. A large number of studies have shown that the pathogenesis of Al-induced AD is mainly related to oxidative stress and autophagy dysfunction [8]. Oxidative stress is strongly thought to play a key role in Al neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Ethanol extract of Andrographis paniculata alleviates aluminum-induced neurotoxicity and cognitive impairment through regulating the p62-keap1-Nrf2 pathway

Ma,

Zheng,

Zhang

et al. 2023

BMC Complement Med Ther

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Background Alzheimer’s disease (AD) is the most prevalent neurodegenerative and remains incurable. Aluminum is a potent neurotoxin associated with AD. The main pathological features of AD are extracellular amyloid-β protein deposition and intracellular hyperphosphorylated Tau protein. A body of evidence suggest that oxidative stress and autophagy are involved in the pathogenesis of AD. Andrographis paniculata (AP) is a native plant with anti-inflammatory, anti-oxidative stress, and regulation of autophagy properties. AP significantly alleviated cognitive impairments, reduced Aβ deposition and has neuroprotective effect. However, its effects on aluminum-induced AD model have not been studied much. In this study, we investigated whether AP protect against aluminum-induced neurotoxicity through regulation of p62-Kelch-like ECH-associated protein 1(Keap1)-Nuclear factor E2 related factor 2 (Nrf2) pathway and activation autophagy in vivo and in vitro. Methods UPLC-ESI-qTOF-MS/MS was used to identify the chemical constituents of AP ethanol extract. The mice with cognitive deficit were established by injecting aluminum chloride and D-galactose, and treated with either AP extract (200, 400, or 600 mg/kg/d) or andrographolide (2 mg/kg/2d).The spatial memory ability was detected by Morris water maze, HE staining were used to detect in brain tissue,Oxidative stress indexs and SOD activity in both serum and brain tissue were detected by kit.The expression of p62-Nrf2 pathway proteins were measured via western blotting. Furthermore, the neurotoxicity model was induced by aluminum maltolate (700 µM) in PC12 cells. Following AP and andrographolide treatment, the cell viability was detected. The relevant mRNA and protein expressions were detected in cells transfected with the p62 siRNA. Results The main active components of AP included andrographolide, neoandrographolide and deoxyandrographolide as identified. AP and andrographolide significantly improved the spatial memory ability of mice, attenuated pathological changes of hippocampal cells, reduced the level of malondialdehyde, and increased superoxide dismutase activity in serum or brain tissue as compared to model control. In addition, the Nrf2, p62 and LC3B-II proteins expression were increased, and p-Tau and Keap1 proteins were decreased in the hippocampus after AP and andrographolide treatment.Furthermore, AP increased aluminum maltolate-induced cell viability in PC12 cells. Silencing p62 could reverse the upregulation expression of Nrf2 and downregulation of Keap1 and Tau proteins induced by AP in aluminum maltolate-treated cells. Conclusions AP had neuroprotective effects against aluminum -induced cognitive dysfunction or cytotoxicity, which was involved in the activation of the p62-keap1-Nrf2 pathway and may develop as therapeutic drugs for the treatment of AD. However, this study has certain limitations, further optimize the protocol or model and study the molecular mechanism of AP improving AD.

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Aluminum neurotoxicity and autophagy: a mechanistic view

Cited by 14 publications

References 120 publications

Aluminum Concentrations in Male and Female Football Players during the Season

Aluminum Concentrations in Male and Female Football Players during the Season

Deciphering the Significance of Metal Ions in the Pathogenesis of Alzheimer's Disease and Forging Pathways Towards Prospective Therapeutic Strategies

Ethanol extract of Andrographis paniculata alleviates aluminum-induced neurotoxicity and cognitive impairment through regulating the p62-keap1-Nrf2 pathway

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