Role of aluminum exposure on Alzheimer’s disease and related glycogen synthase kinase pathway

Sanajou, Sonia; Erkekoğlu, Pınar; Şahin, Gönül; Baydar, Terken

doi:10.1080/01480545.2022.2065291

Cited by 16 publications

(15 citation statements)

References 85 publications

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“…Long-term environmental or occupational exposure to Al is associated with several neurophysiologic processes responsible for AD's characteristic degeneration [8]. In the brain, chronic exposure to Al may lead to biochemical and pathological changes such as oxidative stress, neuroin ammation, increase in amyloid beta (Aβ) plaques, hyperphosphorylation of Tau proteins, apoptosis cholinergic dysfunction, and mitochondrial dysfunction [9,10]. Downregulation of the Wnt/-catenin pathway (named Wnt signaling) and overexpression of GSK3 have been linked to AD [9,11].…”

Section: Introductionmentioning

confidence: 99%

“…In the brain, chronic exposure to Al may lead to biochemical and pathological changes such as oxidative stress, neuroin ammation, increase in amyloid beta (Aβ) plaques, hyperphosphorylation of Tau proteins, apoptosis cholinergic dysfunction, and mitochondrial dysfunction [9,10]. Downregulation of the Wnt/-catenin pathway (named Wnt signaling) and overexpression of GSK3 have been linked to AD [9,11]. Wnt signaling controls embryo development, cell survival, cellular metabolism, amyloid beta (Aβ) formation, and neurogenesis loss [12].…”

Section: Introductionmentioning

confidence: 99%

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Antioxidant dihydrolipolic acid protects against aluminum-induced toxicity in Alzheimer's model

Sanajou

Yirün

Demirel

et al. 2023

Preprint

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Dihydrolipoic acid (DHLA) is a natural antioxidant that is recognized as being useful in combating metal toxicity and oxidative stress. It can protect cells from environmental contaminants and may be beneficial in treating neurodegenerative diseases by protecting against oxidative damage and chronic inflammation. Therefore, this study aimed to investigate the possible neuroprotective effects of DHLA against aluminum-induced toxicity in an in vitro Alzheimer’s disease (AD) model. The study focused on the glycogen synthase kinase3 (GSK3) pathway, and the Wnt signaling. A differentiated SH-SY5Y cell line model of AD was developed, and the study groups were as follows: control, Al, DHLA, Al-DHLA, AD, AD-Al, AD-DHLA, and AD-Al-DHLA. The impact of DHLA on oxidative stress parameters was evaluated, and GSK3 pathway was evaluated by measuring GSK3-β, human serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA), protein phosphatase 2A (PP2A) levels, and human RAC-alpha serine/threonine-protein kinase (AKT1). The Wnt signaling pathway was evaluated by measuring canonical Wingless and Int-1/β-catenin (Wnt/β-catenin) on different study groups. Exposure to DHLA reduced oxidative stress by dramatically lowering reactive oxygen species levels, protecting against protein oxidation, and limiting malonaldehyde production. Additionally, the total antioxidant capacity of DHLA-treated groups increased drastically. Furthermore, upregulation of Wnt signaling and downregulation of GSK3 pathways were observed in the groups treated by DHLA. Overall, the neuroprotective effects of DHLA, especially by reducing oxidative stress and regulating key imbalanced pathways in AD disease, make it a good candidate to be added to AD patients' treatment regimens.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antioxidant dihydrolipolic acid protects against aluminum-induced toxicity in Alzheimer's model

Sanajou

Yirün

Demirel

et al. 2023

Preprint

Self Cite

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“…Furthermore, α‐LA and DHLA protect cells from As and Cd toxicity by activating the Nrf2 pathway, affecting mTOR signaling, promoting the upregulation of Akt, preventing DNA fragmentation, and safeguarding against cell death (Hossain et al, 2021). Aluminum (Al) is a neurotoxic metal that pervasively spreads in the environment (Sanajou et al, 2023). It is also found in numerous food products as a contaminant or preservative (Ding et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant dihydrolipolic acid protects against in vitro aluminum‐induced toxicity

Sanajou

Yirün

Demirel

et al. 2023

J of Applied Toxicology

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Dihydrolipoic acid (DHLA) is a natural antioxidant known for its ability to counteract metal toxicity and oxidative stress. It has shown the potential to safeguard cells from harmful environmental substances. It may hold therapeutic benefits in treating neurodegenerative disorders by defending against oxidative damage and chronic inflammation. Thus, this study aimed to explore the potential neuroprotective effects of DHLA against aluminum (Al)‐induced toxicity using an Alzheimer's disease (AD) model in vitro. The study focused on two important pathways: GSK‐3β and the Wnt signaling pathways. The SH‐SY5Y cell line was differentiated to establish AD, and the study group were as follows: control, Al, DHLA, Al‐DHLA, AD, AD‐Al, AD‐DHLA, and AD‐Al‐DHLA. The impact of DHLA on parameters related to oxidative stress was assessed. The activity of the GSK‐3β pathway was measured by evaluating the levels of PPP1CA, PP2A, GSK‐3β, and Akt. The Wnt signaling pathway was assessed by measuring Wnt/β‐catenin in the different study groups. Exposure to DHLA significantly reduced oxidative stress by effectively decreasing the levels of reactive oxygen species, thereby protecting against protein oxidation and limiting the production of malonaldehyde. Moreover, the DHLA‐treated groups exhibited a remarkable increase in the total antioxidant capacity. Furthermore, the study observed an upregulation of the Wnt signaling pathway and a downregulation of the GSK‐3β pathway in the groups treated with DHLA. In summary, the neuroprotective effects of DHLA, primarily achieved by reducing oxidative stress and modulating critical imbalanced pathways associated with AD, indicate its potential as a promising addition to the treatment regimens of AD patients.

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“…These metals accumulate in the BSFL and may spread along the food chain [ 9 ], which leads to adverse effects on subsequent resource utilization. Al is a metal that widely exists in nature and has neurotoxicity [ 10 ] and skeletal toxicity to humans [ 11 ]. Different from the previous conclusion [ 12 ], the accumulation of Al in BSFL was found in this study and the accumulated Al in BSFL increased with the increase in the Al addition.…”

Section: Introductionmentioning

confidence: 99%

Toxic Effects of Industrial Flocculants Addition on Bioconversion of Black Soldier Fly Larvae (Hermetia illucens L.)

Zhang

Chen

Yang

et al. 2022

Insects

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Black soldier fly is a saprophagous insect that has been widely reported in recent years due to its excellent performance in bioremediation. Due to the widespread presence of flocculants in the organic waste treated by black soldier fly larvae, this study aimed to evaluate the potential impacts and risks of flocculant addition (a combination of poly aluminum chloride and polyacrylamide with the ratio of 50:1). Results showed that the growth and weight of BSFL in the high-exposure groups (≥200 mg/L) were inhibited. The bioaccumulation of aluminum (Al) in larvae was estimated, and the proportions of different Al forms in the frass from high to low were the residual state (41.38 to 67.92%), water-soluble state (16.88 to 37.03%), acid-soluble state (8.45 to 18.72%), and alkali-soluble state (3.38 to 5.14%). The relative abundance of bacterial genera related to lipid metabolism decreased with increasing flocculant concentrations while disease-related taxa increased in relative abundance. The results serve as a reference for subsequent research and application of the treatment of flocculant-contaminated waste by BSFL.

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Role of aluminum exposure on Alzheimer’s disease and related glycogen synthase kinase pathway

Cited by 16 publications

References 85 publications

Antioxidant dihydrolipolic acid protects against aluminum-induced toxicity in Alzheimer's model

Antioxidant dihydrolipolic acid protects against aluminum-induced toxicity in Alzheimer's model

Antioxidant dihydrolipolic acid protects against in vitro aluminum‐induced toxicity

Toxic Effects of Industrial Flocculants Addition on Bioconversion of Black Soldier Fly Larvae (Hermetia illucens L.)

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