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PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Schematic representation of signaling pathways common to AD and DM induced by GLP-1R agonism.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
These include AMPK, PI3K/AKT, CaMKK2-AMPK, NF-κB, insulin/IGF-1 R and the mitochondrial signaling pathway.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Insulin resistance in the brain perpetuates neuroinflammation, tau hyperphosphorylation, and amyloid pathology in AD and is therefore a driver of neurodegenerative disease (Hölscher, 2019).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
This has led some researchers to refer to AD as “type 3 diabetes” because of the similarities between the impaired brain insulin signaling observed in AD and the insulin resistance observed in T2DM (see below) (de la Monte, 2014; Steen et al., 2005).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
However, this nomenclature has been controversial, with some scholars arguing that categorizing AD as “type 3 diabetes” may be conceptually misleading (Talbot and Wang, 2014; Li et al., 2024).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
The traditional classification of DM is mainly based on abnormalities in insulin secretion and action, such as type 1 DM due to an absolute lack of insulin secretion and T2DM due to insulin resistance and relative insulin deficiency.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
However, the inclusion of abnormal insulin metabolism in the brain as part of “type 3 diabetes” is a break from conventional wisdom and therefore has not yet been agreed upon in the academic community.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Firstly, some people believe that cerebral insulin resistance in patients with AD may not be insulin resistance in the true sense of the word but may instead arise from dysfunctional insulin transport across the BBB and that this transport defect may be caused by abnormal BBB function indirectly resulting from peripheral insulin resistance (Arnold et al., 2018).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Second, existing animal models have significant limitations.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Although rodent models provide important tools for AD research, it is difficult for these models to fully simulate the complex pathophysiological processes of human AD because of the significant differences in brain structure, metabolic characteristics, and immune responses between humans and experimental animals (Qian et al., 2024).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
However, abnormal desensitization of insulin signaling has been observed in the brain tissue of patients with AD even in the absence of DM (Frölich et al., 1998).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Multiple parallels between impaired brain insulin signaling in AD and insulin resistance in T2DM have been reported.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Insulin and insulin-like growth factor-1 (IGF-1) play important roles in cognitive performance, neurological function, and the control of neurogenesis and synaptogenesis (Choi et al., 2025).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Insulin-degrading enzymes (IDEs) are enzymes used to break down insulin and IGF-1, removing Aβ40 and Aβ42 monomers but not affecting Aβ oligomers or fibers (Kemeh and Lazo, 2023).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In an insulin-resistant milieu, insulin may competitively inhibit IDE, which impedes the degradation of Aβ proteins, increases their neurotoxicity, and contributes to the onset of AD (Scherer et al., 2021; Ochiai et al., 2021).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In the state of brain insulin resistance, insulin signaling pathways such as the PI3K/Akt pathway become abnormal, and abnormalities in insulin signaling pathways lead to a decrease in Aβ clearance, which promotes Aβ deposition (Zheng and Wang, 2021).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In addition, brain insulin resistance affects tau metabolism and promotes the hyperphosphorylation of tau proteins, tau protein aggregation, the formation of paired helical filaments, and the further formation of NFTs (Mohandas et al., 2009).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1, as an insulin-promoting hormone, has functional and growth factor properties similar to those of insulin and IGF-1 (Bhalla et al., 2022).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1R, as its receptor, can bind to GLP-1 to exert its growth factor effects.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In addition, Aβ has a tertiary structure similar to that of insulin, peripheral Aβ acts as a negative regulator of insulin secretion, and there can be interactions between Aβ and insulin signaling (You et al., 2022).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Brain insulin resistance is an important pathogenetic feature of AD and is mediated primarily by impaired insulin signaling (Sêdzikowska and Szablewski, 2021).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In a study using the GLP-1R agonist liraglutide, its ability to reverse cognitive deficits in an AD model and its potential neuroprotective mechanisms were identified.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Liraglutide not only blocks insulin receptor and synaptic loss in the brain but also reverses memory impairment induced by AD-associated Aβ oligomers, suggesting that GLP-1R activation may be used to protect brain insulin receptors and synapses in AD (Batista et al., 2018).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In addition, GLP-1R stimulation activates insulin signaling pathways and regulates gene expression, decreasing systemic insulin resistance and brain insulin resistance in patients with AD (Dahiya et al., 2025).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Moreover, because GLP-1R is expressed throughout the body, stimulation with a GLP-1R agonist or indirectly with a DPP-IV inhibitor can have a broad systemic effect on systemic metabolism, which, in turn, ameliorates peripheral and central insulin resistance in AD and MD (Athauda and Foltynie, 2016).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Therefore, it is reasonable to believe that GLP-1R is a potential link between these two diseases.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
AD and DM are significantly associated with neuroinflammatory mechanisms.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Chronic low-grade inflammation is a common pathological feature of both: metabolic disturbances in patients with DM induce the release of peripheral inflammatory factors, and these inflammatory factors pass through the compromised BBB into the central nervous system (CNS), activating microglia and astrocytes and triggering a neuroinflammatory cascade response, which in turn promotes Aβ deposition in AD and tau protein hyperphosphorylation (Sebastian Monasor et al., 2020; Chen et al., 2024).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In addition, obesity-associated adipose tissue inflammation further exacerbates CNS inflammation, creating a vicious cycle of “metabolism–inflammation–neurodegeneration” (Chen et al., 2024; Wong et al., 2024).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1R plays a multidimensional role in regulating neuroinflammation.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Firstly, through a systematic review and network meta-analysis, researchers have assessed the effects of GLP-1R agonists on neuroinflammation and reported that, compared with placebo, GLP-1R agonists significantly reduce the levels of neuroinflammatory markers, such as TNF-α and interleukin-1β (Urkon et al., 2025; Zhang et al., 2022; Tseng et al., 2025).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Second, GLP-1R activation enhances neurovascular coupling function, improves cerebral blood flow and repairs BBB integrity, blocking the penetration of peripheral inflammatory factors into the center (Wong et al., 2024).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Preclinical studies have also revealed that dual agonists of GLP-1R and glucose-dependent insulinotropic polypeptide receptor (GIPR) have synergistic anti-inflammatory and neuroprotective effects, suggesting the potential advantages of multitargeting strategies (Yuan et al., 2024).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1R-targeted therapies have now expanded from metabolic diseases to AD.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
A team of researchers developed a nanostructure-based GLP-1R agonist capable of crossing the BBB that significantly attenuated neuroinflammation and memory loss in an Aβ peptide-induced mouse model of AD by inhibiting the inflammatory responses of microglia and astrocytes (Zhao et al., 2022).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
These findings not only reveal the potential of GLP-1R as a common therapeutic target for AD and DM but also provide a theoretical basis for the development of novel therapies based on the “metabolic–immune–neurological” axis.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Chronic hyperglycemia in patients with T2DM leads to peripheral insulin resistance, whereas impaired insulin signaling pathways in the brains of patients with AD lead to “brain insulin resistance,” both of which are closely related to mitochondrial dysfunction and OS (Du et al., 2022; Zhang et al., 2023).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Mitochondria are the primary site of energy metabolism and reactive oxygen species (ROS) production.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Hyperglycemia exacerbates mitochondrial electron transport chain (ETC) dysfunction and increases ROS production through advanced glycation end products and inflammatory pathways (Zhang et al., 2023; Caturano et al., 2023).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Overproduction of ROS triggers OS (Luna-Marco et al., 2023).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Interestingly, defects in mitochondrial energy metabolism are also present in the brains of patients with AD, leading to neuronal apoptosis and Aβ deposition, which increases ROS production by interfering with mitochondrial calcium homeostasis and ETC function; the hyperphosphorylation of tau proteins leads to the disruption of microtubule structure and affects mitochondrial axonal transport, exacerbating the neuronal energy crisis (Meng et al., 2024).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Activated microglia in patients with AD release proinflammatory factors, which further promote ROS production, creating a vicious cycle of neuroinflammation and mitochondrial dysfunction (Qian et al., 2025).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1R can restore the mitochondrial membrane potential, promote ATP production, and reduce ROS production by activating the cAMP/PKA pathway (Signorile et al., 2022).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In addition, activation of GLP-1R regulates mitochondrial over fission by the cAMP/PKA pathway while improving mitochondrial function in Aβ-treated astrocytes and ameliorating pathological lesions in AD (Xie et al., 2021).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Clinical studies have shown that GLP-1R reduces ROS levels, the mitochondrial membrane potential and mitochondrial apoptosis in patients with diabetes (Durak and Turan, 2023; Wang et al., 2021), as well as alleviating levels of OS and attenuating low-grade inflammation (Zhang et al., 2018).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1R reduces oxidative damage accumulation by modulating autophagy-related proteins and scavenging damaged mitochondria while increasing superoxide dismutase (SOD) and glutathione peroxidase activities, reducing the generation of lipid peroxidation products, inhibiting the NF-κB signaling pathway, and decreasing proinflammatory factor expression to reduce neuroinflammation (Ma et al., 2018; Lin et al., 2021).
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In conclusion, GLP-1R plays important roles in mitochondrial dysfunction and OS in AD and DM.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
The treatment of AD faces serious challenges, and the incidence of this disease is increasing every year, placing a heavy burden on global health.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Despite the never-ending exploration of AD, our understanding of the disease remains limited, especially in terms of etiology and pathogenesis.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Recent studies suggest that GLP-1R may be an important link between DM and AD.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Evidence suggests that GLP-1R agonists, initially developed for the treatment of DM, have therapeutic potential in the management of AD because of their multifaceted mechanism of action.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1R agonists exhibit neuroprotective effects in AD, including anti-inflammatory effects, modulation of Aβ deposition and clearance, improved insulin signaling, and attenuation of OS.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
The intersection between DM and AD further highlights the shared pathophysiological mechanisms, particularly the disruption of insulin signaling pathways in the brain.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
This disruption is referred to as “type 3 diabetes” and is characterized by neuroinflammation, cognitive deficits, and amyloid pathology, which are common to both DM and AD.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1R may ameliorate these conditions by improving insulin signaling and reducing insulin resistance in the brain.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Although GLP-1R agonists have yielded promising results in animal models, AD transgenic mice do not fully mimic the complex pathology of human AD, and there are still some challenges in translating them into effective AD therapies.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
For example, limitations in BBB penetration efficiency allow for limited distribution in the CNS, which may affect efficacy.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Current studies suggest that peripherally administered GLP-1RA has low concentrations in the cerebrospinal fluid, and higher doses or improved delivery systems (e.g., nanoparticles, liposome encapsulation) may be needed to increase brain exposure.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In addition, there are potential risks and limitations associated with GLP-1R therapy.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Most GLP-1R agonists have gastrointestinal side effects, including nausea, vomiting, diarrhea and constipation, which may be more pronounced in elderly patients with AD and affect treatment compliance.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Whether long-term use leads to risks such as hypoglycemia and thyroid C-cell hyperplasia remains to be further evaluated.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
However, novel drug delivery systems or formulations may be able to reduce the risk of gastrointestinal side effects and hypoglycemia.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
With the in-depth theory of the gut–brain GLP-1R axis, the breakthrough of new material technology and the rapid development of AI-assisted drug design, GLP-1R-related research has also ushered in new opportunities.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
An in-depth analysis of the signaling mechanism of GLP-1R in the gut–brain GLP-1R axis is needed to aid in developing smarter new material delivery systems to achieve precise targeting and long-lasting release of GLP-1R agonists.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Moreover, AI technology can be used to accelerate the design and screening of novel GLP-1R agonists to promote personalized therapy.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
In conclusion, GLP-1R signaling represents a promising therapeutic strategy that bridges the treatment of DM and AD.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Its potential to modulate metabolic and neuroprotective pathways offers hope for the development of new therapies that could improve the prognosis of patients with both diseases.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
GLP-1R is not only a key target for metabolic regulation but also a bridge between metabolism and the nervous system.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
With further research and technological advances, GLP-1R agonists are expected to become the core drugs for the treatment of AD and DM.
PMC12328308
GLP-1R as a potential link between diabetes and Alzheimer’s disease
Future studies should continue to explore the dual mechanism of action of GLP-1R in metabolism and the nervous system, especially its potential applications at the intersection of AD and DM.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Alzheimer’s disease (AD) was a progressive neurodegenerative disorder characterised by an insidious onset and gradual cognitive decline.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
It remained a significant global health challenge.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Methylparaben (MEP), a preservative commonly used in cosmetics and food processing, had been associated with the development and progression of AD.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
First, we acquired the initial three-dimensional (3D) structure of MEP from PubChem (CID: 7456), followed by structural optimization via energy minimization using Chem3D software to complete its 3D structural characterisation.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
This was followed by systematic target prediction across the SwissTargetPrediction, SEA, GeneCards and OMIM databases.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
We then constructed protein-protein interaction (PPI) networks using STRING and visualised them in Cytoscape to identify core targets.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Molecular docking simulations using CB-Dock2 elucidated the binding affinities between MEP and the key proteins.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Experimental validation combined Gene Expression Omnibus (GEO) database analysis with quantitative reverse transcription polymerase chain reaction (qRT-PCR) to quantify transcriptional changes in SK-N-SH neural cells.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
A total of 153 potential targets associated with MEP and AD were identified.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Ten core targets were determined through screening using the STRING platform and Cytoscape software, including HIF1A, IGF1R, PDGFRB, PTK2, VCAM1, CXCL12, ERBB2, ESR1, JAK2 and BCL2L1.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the core MEP targets in AD primarily concentrate on the following key signalling pathways: Neuroactive ligand-receptor interactions, EGFR tyrosine kinase inhibitor resistance, HIF-1 signalling pathway and gamma-aminobutyric acid (GABA) synapse.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Molecular docking simulations using CB-Dock2 confirmed a high binding affinity between MEP and these core targets.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
To investigate the mechanism of action of MEP, we validated the findings using clinical datasets and the human neuroblastoma cell line SK-N-SH.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Upregulation of ten transcriptional expressions was observed, suggesting that MEP might influence cognitive function in patients with AD.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
This study elucidated the potential molecular mechanisms of MEP in the progression of Alzheimer’s disease-related tau pathology, offering new insights for the prevention and intervention of degenerative diseases that might be triggered by excessive exposure to MEP environments.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Alzheimer’s disease (AD) was recognised as the most prevalent form of dementia.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
It was a progressive neurodegenerative disorder that poses a significant challenge to global public health in contemporary society .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
This devastating condition was characterised by a gradual deterioration of cognitive function, persistent memory impairment and a progressive loss of independence when performing daily activities.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
It profoundly compromised patients’ quality of life and imposes a substantial socio-economic burden on affected families .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
According to the latest estimates from the World Health Organization (WHO), the global prevalence of AD currently affected approximately 50 million individuals.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Epidemiological projections indicated that this figure was likely to double by 2050 .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
These staggering statistics highlighted the significant social and economic burdens that were expected to emerge in the coming decades.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
The etiopathogenesis of AD was characterized by its multifactorial nature, involving an intricate interplay between genetic predisposition, environmental determinants, and lifestyle factors .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Contemporary research had established that the hallmark neuropathological features of AD primarily include the cerebral accumulation of β-amyloid plaques and the formation of neurofibrillary tangles composed of hyperphosphorylated tau proteins .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
These pathological alterations precipitated neuronal apoptosis and synaptic dysfunction, ultimately culminating in progressive cognitive deterioration .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Furthermore, emerging evidence highlighted the critical role of neuroinflammation, oxidative stress mechanisms, and blood-brain barrier dysfunction in accelerating AD progression .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Numerous studies had also indicated that a healthy diet is a key factor in reducing the risk of Alzheimer’s disease .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Methylparaben (MEP) was a compound of particular interest in this context, given its status as a ubiquitous environmental endocrine disrupter.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
It was widely used as a preservative in personal care products, pharmaceuticals and food formulations.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
It also occurred naturally in various fruits and vegetables .