Aluminum (Al) is an environmentally abundant metal that is not essential for life. There is considerable evidence that Al as a neurotoxic xenobiotic may play a role in the pathogenesis of neurodegenerative diseases like Alzheimer’s disease (AD). Exposure to aluminum has been shown to cause neuronal damage that resembles the symptoms of AD. In this review, we will summarize recent data about Al as the possible risk of incidence of AD. Then glycogen synthase kinase-3 beta (GSK3β) contributes to the hyperphosphorylation of Tau protein, the main component of neurofibrillary tangles, one of the hallmarks of AD as one of the mechanisms behind Al neurotoxicity will be covered. Overall, there is still a need for epidemiological studies and more in vivo and in vitro studies to determine the exact mechanisms of its neurotoxicity and the role of GSK3β in both Al toxic effect and AD.

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.

Alzheimer's disease (AD) is a progressive neurological disorder that affects various cognitive functions, behavior, and personality. AD is thought to be caused by a combination of genetic and environmental factors, including exposure to aluminum (Al). Virgin coconut oil (VCO) may have potential as a natural neuroprotectant against AD. Aim of this study was to determine neuroprotective effects of VCO on Al‐induced neurotoxicity in an in vitro AD model. SH‐SY5Y cells were initially cultured in normal growth medium and then differentiated by reducing fetal bovine serum content and adding retinoic acid (RA). Later, brain‐derived neurotrophic factor (BDNF) was added along with RA. The differentiation process was completed on the seventh day. Study groups (n = 3) were designed as control group, VCO group, Al group, Al‐VCO group, Alzheimer model (AD) group, AD + Al‐exposed group (AD+Al), AD + VCO applied group (AD + VCO) and AD + Al‐exposed + VCO applied group (AD + Al + VCO). Specific markers of AD (hyperphosphorylated Tau protein, amyloid beta 1–40 peptide, and amyloid precursor protein) were measured in all groups. In addition, oxidative stress parameters (total antioxidant capacity, lipid peroxidase, protein carbonyl, and reactive oxygen species) and neurotransmitter‐related parameters (dopamine, dopamine transporter acetylcholine, and synuclein alpha levels, acetylcholinesterase activity) were measured comparatively in the study groups. VCO reduced amyloid beta and hyperphosphorylated Tau protein levels in the study groups. In addition, oxidative stress levels decreased, and neurotransmitter parameters improved with VCO. Our study shows that VCO may have potential therapeutic effects in Alzheimer's disease and further experiments are needed to determine its efficacy.