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PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The synthesized cDNAs were stored at −20 °C until RT-PCR.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Expression levels of apoptosis-related genes at the mRNA level in the control and dose group cells were evaluated using a real-time PCR system (Rotor Gene, Qiagen, USA).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
SYBR Green, which can bind to double-stranded DNA, was used as the dye.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The reaction was completed with 5X SYBR Green mixture, 5 pMol forward (F), 5 pMol reverse primer (R), 2 μL cDNA, and sterile RNase–DNase-free water to a final concentration of 1X, and the reaction was carried out in sterile 8-well PCR strips.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The temperature profile of the reaction was adjusted to 95 °C for 15 min and then 40 cycles (95 °C for 15 s, 60 °C for 20 s, and 72 °C for 20 s) took place.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Then, the heating process was carried out gradually from 60 °C to 95 °C with 0.5 °C increments, and optical measurements were made at each 0.5 °C increment in temperature to create the melting curve graph via melting curve analysis.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The data obtained from the optical analysis in real-time PCR were recorded as “Ct” (cycle of threshold), and the expression levels of the target genes were normalized with the GAPDH reference gene.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The sequences were obtained from the OriGene (https://www.origene.com, accessed on 1 October 2023) online web page.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
All statistical analyses were performed using SPSS software (Statistical Package for the Social Sciences version 21, Chicago, IL, USA).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Real-time PCR data were analyzed using the ΔΔCT method and quantification was performed with the help of a computer program.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Volcano plot analyses in the web-based “RT Profiler™ PCR Array Data Analysis” program were used.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The method was based on the comparison of two expression results ±3SD.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Thus, in cases where gene expression was compared, the expression values of relevant genes in the control and dose groups were determined relatively.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The comparison of the groups was evaluated statistically using the “Student t-test” analysis in the “RT Profiler™ PCR Array Data Analysis” program.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Continuous variables are given as mean ± standard deviation, and categorical variables are given as a number and percentage.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
A p-value of <0.05 was considered statistically significant.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The effects of various concentrations on cell viability in SH-SY5Y human neuroblastoma cell lines to which P. sidoides extract was applied at 24 and 48 h are shown in Figure 1.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
While cell viability in the control group cells was accepted as 100%, cell viability decreased significantly at the end of 24 h at a concentration of 50 µg/mL of the extract to approximately 70% (p < 0.05).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
A gradual decrease in cell viability was observed depending on the increasing concentrations of the extract: Cell viability decreased to 65% at a concentration of 100 µg/mL (p < 0.05); viability decreased to 55% at a concentration of 200 µg/mL (p < 0.05); viability decreased around 50% at 400 µg/mL; and viability decreased to 40% at a concentration of 800 µg/mL (p < 0.05).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
A similar trend was observed during the 48 h incubation period, and it was determined that the cytotoxic effect of P. sidoides continued stably as time progressed.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
These findings provide support that P. sidoides root extract significantly reduced cell viability in a dose- and time-dependent manner, and the IC50 value was 113.83 µg/mL (Figure 1).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The IC50 value was calculated to be 113.83 μg/mL at 24 h. The IC50 (113.83 μg/mL) value determined as the dose group was used in the following experimental steps.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The protein concentrations of the control group SH-SY5Y cells and the P. sidoides extract dose group (113.83 μg/mL) cells were compared with the 8-Hydroxy-deoxyguanosine ELISA test.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The concentration calculation was analyzed according to Figure 2 and this value was determined as 1.1397 ng/mL in the control group, while this value was determined as 1.4815 ng/mL in the extract dose group (p < 0.05) (Figure 2).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
These results show us that the concentration of 8-Hydroxy-deoxyguanosine, one of the important oxidative stress and genotoxicity markers, increased in neuroblastoma cells as a result of P. sidoides extract treatment (p < 0.05).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This result indicates that P. sidoides extract may have increased the possible oxidative stress and genotoxic effect in the cell and led to cell death.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
When the control and P. sidoides group cells were compared, the TAS value was 0.3455 mMOL Trolox Equiv./L for the control group, while it was 0.2915 mMOL Trolox Equiv./L in the P. sidoides dose group cells.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This result shows that the total antioxidant activity in SH-SY5Y cells treated with P. sidoides extract was partially reduced (p > 0.05) (Figure 3).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
When the control and P. sidoides group cells were compared, the TOS value was determined as 2.9463 µmol H2O2 equiv./L for the control group, while it was 5.6370 µmol H2O2 equiv./L in the P. sidoides group cells.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This result shows that the total oxidant activity increased in neuroblastoma cells treated with P. sidoides extract (p < 0.01) (Figure 4).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The OSI values are shown in Figure 5.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
OSI levels increased in cells treated with P. sidoides extract (p < 0.001).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
While the OSI value was determined to be approximately 0.9 in the control group, this value increased to 1.8 in the P. sidoides group (Figure 5).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The gene expression fold changes in the P. sidoides dose group and control group SH-SY5Y cells are shown in Table 1.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
BAX gene expression, caspase-3 expression, caspase-8 expression, and caspase-9 gene expression increased 2.93, 3.31, 4.34, and 2.41-fold in the P. sidoides dose group compared to the control at the mRNA level, respectively.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Among these changes, the BAX and Caspase-8 expression increases were statistically significant in the P. sidoides dose group (p < 0.05).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
There was no significant change in Bcl-2 gene expression (Table 1).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This study comprehensively examined the effects of P. sidoides root extract on human neuroblastoma cell line (SH-SY5Y).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The findings show that P. sidoides extract can inhibit cell proliferation and increase oxidative stress and genotoxic effects, leading to cell death.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In our study, the XTT test results revealed that P. sidoides significantly reduced cell proliferation at the dose where it reached the IC50 value.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This supports the anticancer potential of the extract.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
P. sidoides is rich in phenolic compounds, which suggests that it activates mechanisms that suppress cell proliferation.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Studies in the literature show that phenolic compounds generally play a role as cell cycle regulators and apoptosis inducers .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Ramirez et al. reported that plant polyphenols can stop the growth of cancer cells by inhibiting the PI3K/Akt and Ras/MAPK signaling pathways .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
P. sidoides is also thought to inhibit cell proliferation in the neuroblastoma cell line through similar mechanisms.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In our study, measurements performed with ELISA revealed that P. sidoides affects DNA damage and is an important indicator of oxidative stress by increasing 8-Hydroxy-deoxyguanosine levels.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
These findings suggest that cell death is induced through oxidative stress and genotoxicity mechanisms.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
It has been stated in the literature that P. sidoides may cause genotoxic effects by increasing oxidative stress levels .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Pereira et al. showed that the phenolic components of P. sidoides extract triggered apoptosis in cancer cells by regulating oxidative stress and increasing reactive oxygen species (ROS) levels .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Similarly, Mates et al. reported that increased oxidative stress leads to DNA damage, which in turn induces apoptosis in cancer cells .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Our study supports these literature findings and shows that P. sidoides may be an effective herbal agent, especially in increasing oxidative stress.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In our study, TAS, TOS and OSI results show that P. sidoides increases total oxidant levels while decreasing antioxidant levels and significantly increases oxidative stress index (OSI).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
These results support the critical role of oxidative stress in inducing apoptosis in neuroblastoma cells.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Increased oxidative stress leads to the accumulation of reactive oxygen species (ROS), causing DNA damage, mitochondrial dysfunction and disruptions in cellular homeostasis .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Yuhang et al. stated that ROS accumulation causes loss of mitochondrial membrane potential and plays a key role in the initiation of apoptosis .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Consistent with these findings, our study shows that P. sidoides triggers apoptosis in neuroblastoma cells by increasing oxidative stress.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In our study, the RT-PCR results revealed significant increases in BAX, caspase-3, caspase-8, and caspase-9 gene expression.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This suggests that both the mitochondrial pathway (BAX) and death receptor-mediated pathways (Caspase-8) are activated.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In particular, high regulation of BAX and caspase-8 leads to the opening of mitochondrial permeability transition pores, supporting cytochrome C release and the subsequent activation of the apoptotic cascade.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
These findings are consistent with the report by Chaudhry et al. that herbal compounds induce apoptosis by activating the BAX and caspase pathways .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In addition, the increased expression of caspase-3 and caspase-9 indicates that apoptosis progresses via the mitochondrial pathway .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
It has been previously reported in the literature that phenolic compounds of P. sidoides promote apoptosis by regulating the expression of these genes .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Young et al. reported that phenolic compounds contribute to the direction of programmed cell death in cancer cells by increasing caspase-3 and caspase-9 activity .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Our study shows that these mechanisms can also be activated by P. sidoides in the neuroblastoma cell line.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In addition, no significant change was observed in Bcl-2 gene expression.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This suggests that anti-apoptotic mechanisms are suppressed and that pro-apoptotic signals become dominant during the apoptosis process.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
It has been frequently stated in the literature that the decrease in the Bcl-2/BAX ratio is a critical indicator for apoptosis .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The observation that this ratio was disrupted in our study is strong evidence of the apoptosis-promoting effect of P. sidoides.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The IC50 value obtained in our study (113.83 µg/mL) is consistent with previous studies.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
For example, Pereira et al. showed the antiproliferative effect of P. sidoides on a leukemia cell line at similar dose ranges .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Similarly, it has been reported that doses in the range of 100–400 µg/mL are generally used in studies for the effects of plant extracts on cancer cells .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This study is one of the first studies to confirm the apoptotic effect of P. sidoides on a neuroblastoma cell line.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In our study, only one cancer cell line (SH-SY5Y) was used.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
However, evaluating the potential cytotoxic effects of plant extracts on healthy cells is critical for treatment efficacy and safety.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In future studies, the selectivity of P. sidoides should be investigated using healthy cell lines (e.g., fibroblast or epithelial cells).
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
It is known that non-selective agents are not suitable for clinical application.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In this study, only the neuroblastoma cell line was examined, and no reference cell line was used.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Comparative analyses with healthy cell lines and different cancer cell lines (such as HeLa or MCF-7) are needed to determine whether apoptosis is specifically induced in cancer cells.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Such analyses will more clearly reveal the targetability and therapeutic potential of P. sidoides.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
While this study demonstrates significant fold changes in gene expression for several apoptosis-related genes in SHSY5Y cells using RT-PCR, one of the limitations is the absence of protein-level validation through Western blot analysis.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Western blotting could provide additional confirmation of changes in protein levels for key genes, such as BAX, Caspase-3, and Caspase-8, as supported by previous studies .
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Future studies should include Western blot analysis to validate these findings at the translational level and further substantiate the apoptotic effects of P. sidoides extract.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
This study investigated the effects of Pelargonium sidoides root extract on human neuroblastoma cell line (SH-SY5Y) to reveal the anticancer potential of this herbal agent.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
The results obtained show that P. sidoides can induce apoptosis by inhibiting cell proliferation and increasing oxidative stress and genotoxicity.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
It was determined that phenolic compounds in particular promote cancer cell death by activating oxidative stress mechanisms and regulating apoptotic pathways.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
Our results indicate that P. sidoides, rich in phenolic compounds, can be evaluated as a complementary agent in the treatment of pediatric cancers, such as neuroblastoma.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
However, further in vivo and clinical studies are needed to evaluate its clinical applicability and safety.
PMC11679892
Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells
In addition, the potential of this herbal agent should be investigated in more detail with different doses, application times, and combined treatment strategies.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
Tau was initially identified as a microtubule-binding protein critical for microtubule stabilization.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
It is also a pathological hallmark of tauopathies, a group of neurodegenerative diseases that include Alzheimer’s disease.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
Under pathological conditions, Tau becomes hyperphosphorylated at numerous sites and aggregates into filamentous deposits, contributing to neuronal cell death and disease progression.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
While significant research has focused on Tau phosphorylation dynamics and their consequences in pathological contexts, comparatively few studies have investigated Tau phosphorylation during physiological processes, despite the potential relevance to the early onset of pathology.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
Previous findings have suggested similarities between mitotic Tau phosphorylation and hyperphosphorylation observed in tauopathies, particularly at sites such as AT8, PHF1, S214, and S422.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
In this study, we quantified the relative levels of phosphorylation at 12 Tau phospho-epitopes during interphase and mitosis in vitro to establish a preliminary mitotic phospho-Tau signature, which was subsequently validated in vivo.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
Our results demonstrated pronounced phosphorylation of Tau at AT8, p-T217, and p-S422 epitopes during mitosis, both in vitro and in vivo.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
These findings provide new insights into the physiological phosphorylation of Tau and its potential links to pathological processes.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
Tau is primarily known as a microtubule-associated protein that stabilizes microtubules in neurons .
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
Phosphorylation of Tau was reported to be associated with a reduced affinity in microtubule binding .
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
This effect is particularly pronounced at phosphorylation sites within the microtubule binding domain, such as S262 and S356 , as well as in other regions.
PMC12562719
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
For example, phosphorylation at S214 within the proline-rich region and at S396 and S404 in the C-terminal domain—phospho-residues that together constitute the PHF1 epitope—also impairs microtubule binding .