Association Between the Endocannabinoid System-Related Gene Variants and Epilepsy.

The endocannabinoid system (ECS) is an intricate network consisting of receptors, enzymes, and endogenous ligands that play a pivotal role in various neurological processes. It has been implicated in the pathophysiology of several neurological disorders, including epilepsy. Extensive research has demonstrated the involvement of genetic factors in influencing the susceptibility to and progression of epilepsy. In this study, we focused on investigating the connection between genetic variations in genes related to the ECS and the occurrence of epilepsy. Some ECS-related gene variants were selected and genotyping was performed using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique. Interestingly, CNR1 rs12720071 genotype (OR 16.33, 95% CI 1.8-149; p = 0.001) showed an association with generalized epilepsy and MGLL rs604300 genotype (OR 2, 95% CI 1.1-3.4; p = 0.013) demonstrated a relationship with females diagnosed with focal epilepsy. So, studying CNR1, MGLL, and their genetic variations provides insights into the role of the endocannabinoid system in health and diseases. Moreover, they hold the potential to pave the way for the development of novel therapeutic approaches specifically targeting them.

Kynurenine and Beta-Alanine Serum Levels are Associated with the Expression of Wnt Pathway Genes in Patients with Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Despite its worldwide prevalence, there is currently no clear explanation for the mechanism of this disease. In addition, the lack of reliable and accurate biomarkers makes the early detection of PD difficult. Therefore, we examined serum beta-alanine and kynurenine levels and expression of Wnt pathway genes in leukocytes from patients with PD. METHODS: Ninety patients, 45 with PD and 45 healthy subjects, were enrolled in this study. Ten milliliters of blood were drawn from all participants. Serum levels of beta-alanine and kynurenine were measured by ELISA, and the expression of Wnt pathway genes in leukocytes was determined by real-time PCR. RESULTS: Serum levels of kynurenine and beta-alanine were higher in PD patients than in the control group. Data analysis also showed that the expression of some Wnt pathway genes was decreased in leukocytes. CONCLUSIONS: The correlation between serum levels of beta-alanine and kynurenine and the expression of the gene that encodes the Wnt signaling pathway in leukocytes was found in patients with PD. As a result, these biomarkers can be utilized for the early detection, monitoring, and treatment of patients with PD.

The Role of Mitochondrial Biogenesis in Ischemic Stroke.

Ischaemic stroke is a sudden neurological disorder caused by localised cerebral ischaemia and persistent cerebral infarction. Occlusion of large arteries due to atherothrombosis, cerebral embolism (i.e., embolic infarction), no thrombotic occlusion in small, deep cerebral arteries (i.e., lacunar infarction), and stenosis of proximal arteries due to hypotension leading to decreased cerebral blood flow in arterial supply zones are the most common causes of ischemic stroke (i.e., hemodynamic stroke). It is now known that organelles play an important role in various signaling events and cellular functions. The molecular mechanisms of mitochondria are involved in cerebral ischemia by generating and scavenging reactive oxygen species, apoptosis, biogenesis, mitochondrial dynamics, and inflammation are all examples of electron transport chain dysfunction. More knowledge about the involvement of mitochondria in ischemia-induced neuronal death and neuronal protection will contribute to the development of better treatment programs for stroke syndromes such as ischemic stroke.

Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model.

Introduction: Alzheimer's disease (AD) is the most common form of dementia worldwide. This study investigated the effects of lipopolysaccharide on neurosteroidogenesis and its relationship to growth and differentiation using SH-SY5Y cells. Methods: In this study, we used the MTT assay to assess the impact of LPS on SH-SY5Y cell viability. We also evaluated apoptotic effects using FITC Annexin V staining to detect phosphatidylserine in the cell membrane. To identify gene expression related to human neurogenesis, we utilized the RT2 Profiler TM PCR array human neurogenesis PAHS-404Z. Results: Our study found that LPS had an IC50 level of 0.25 µg/mL on the SH-SY5Y cell line after 48 h. We observed Aß deposition in SH-SY5Y cells treated with LPS, and a decrease in DHT and DHP levels in the cells. Our analysis showed that the total rate of apoptosis varied with LPS dilution: 4.6% at 0.1 µg/mL, 10.5% at 10 µg/mL, and 44.1% at 50 µg/mL. We also observed an increase in the expression of several genes involved in human neurogenesis, including ASCL1, BCL2, BDNF, CDK5R1, CDK5RAP2, CREB1, DRD2, HES1, HEYL, NOTCH1, STAT3, and TGFB1, after treatment with LPS at 10 µg/mL and 50 µg/mL. LPS at 50 µg/mL increased the expression of FLNA and NEUROG2, as well as the other genes mentioned. Conclusion: Our study showed that LPS treatment altered the expression of human neurogenesis genes and decreased DHT and DHP levels in SH-SY5Y cells. These findings suggest that targeting LPS, DHT, and DHP could be potential therapeutic strategies to treat AD or improve its symptoms.

The study of rs324420 (C385A) polymorphism of the FAAH gene of the endocannabinoid system in patients with epilepsy and ADHD.

The endocannabinoid (eCB) system regulates many physiological functions in the central nervous system. Fatty acid amide hydrolase (FAAH) is an essential enzyme in the eCB system, degrading anandamide. Single nucleotide polymorphism (SNP) rs324420 is a common genetic polymorphism of the FAAH gene and has been associated with susceptibility to neurological conditions. This study examined whether the SNP rs324420 (C385A) is associated with epilepsy and attention deficit hyperactivity disorder (ADHD). This study consists of two case-control parts. The first part comprises 250 epilepsy subjects and 250 healthy individuals as controls. The second one comprises 157 cases with ADHD and 136 healthy individuals as controls. Genotyping was carried out using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique. Interestingly, the FAAH C384A genotype (OR 1.755, 95 % CI 1.124-2.742, p = 0.013) and allele (OR 1.462, 95 % CI 1.006-2.124, p = 0.046) distribution showed an association with generalized epilepsy. On the other hand, this SNP was not associated with the risk of ADHD. To our knowledge, there was no study on the association between rs324420 (C385A) polymorphism and the risks of ADHD or epilepsy. This study provided the first evidence of an association between generalized epilepsy and rs324420 (C385A) of FAAH. Larger sample sizes and functional studies are warranted to explore the clinical utility of FAAH genotyping as a possible marker for increased generalized epilepsy risk.

Diagnostic Value of ATG5, Apo-Lipoprotein B-48, Thyroid Hormones, and Homocysteine in Patients with Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia. In this study, serum levels of autophagy-related 5 (ATG5), apolipoprotein B-48, thyroid hormones, and homocysteine were examined in patients with AD to determine their diagnostic and predictive value for early diagnosis and prevention of AD. MATERIALS: For this study, fifty serum samples were obtained from patients with AD and fifty serum samples from healthy controls. Serum levels of ATG 5, apo B48, thyroid hormones, homocysteine, vitamin B12, and folic acid were determined by ELISA. Spectrophotometry was used to determine serum lipid concentrations. RESULTS: The mean age of the case group was 69 ± 6.4 years and that of the control group was 67 ± 4.2 years. There were differences between the control and case groups in serum levels of homocysteine, apo B48, ATG5, hsCRP, LDL, HDL, cholesterol, and VitB12 (p < 0.05). According to the results of the ROC curve, measurements of serum levels of ATG5, homocysteine, and apo B48 have excellent performance in distinguishing patients with Alzheimer's disease from patients without AD. CONCLUSIONS: This study suggests that the measurement of serum levels of ATG5, homocysteine, and apo B48, along with other available biomarkers, can be helpful in the diagnosis and management of patients with AD in the early stages of their disease.

Diagnostic Potential of Autophagy-5 Protein, Apolipoprotein B-48, and Oxidative Stress Markers in Serum of Patients with Early-Stage Ischemic Stroke.

OBJECTIVE: Strokes are among the leading causes of death worldwide and have different characteristics. Different physiopathological mechanisms characterize the numerous subtypes of ischemic stroke (IS). In this study, we investigated the relationship between serum levels of autophagy-5 protein, apolipoprotein B-48, and oxidative stress markers in patients with ischemic stroke. METHODS: For this study, 100 participants were recruited, of which 50 were patients with IS and 50 were healthy individuals. We conducted a case-control study at Imam Reza Hospital from March 2019 to April 2020. Serum levels of ATG5, apo B-48, and oxidative stress markers were determined in both groups. Our Receiver Operating Characteristic Analysis evaluated the additional diagnostic value of these factors in both groups. RESULTS: Diabetes, smoking, age, sex, alcohol consumption, weight, and height did not differ significantly between the 2 groups (P > 0.05). However, the 2 groups had significant differences in hypertension and body mass index (P < 0.05). Fifty-four percent (27 patients) of patients with IS had an ischemic stroke in large vessels, while 46% (23 patients) had an ischemic stroke in small vessels. Serum levels of ATG5, apo B-48, and oxidative stress markers were higher in the case group than in the control group (P < 0.0001). CONCLUSIONS: In patients with IS, serum levels of ATG5, apoB-48, malonaldehyde, total oxidative stress, and total antioxidant capacity can be used as novel biomarkers to predict or treat the disease.

Evaluation of the Diagnostic and Predictive Value of Glutamic Acid Decarboxylase, Zinc Transporter 8 Serum Levels in Alzheimer's Disease.

BACKGROUND: Identification of validated peripheral biomarkers for Alzheimer's Disease, leading to an early diagnosis of the disease, would be valuable for predicting progression and targeted therapeutics. In this regard, serum levels of GADA, ZnT8A, Zn, vitamin D, and leukocyte expression of brain-derived neurotrophic factor (BDNF) gene were investigated in Alzheimer's patients and control group. METHODS: Serum levels of GADA, ZnT8A, Zn, and vitamin D and leukocyte expression of the BDNF gene were evaluated in 40 AD patients and 40 control cases. The diagnostic value of investigated factors was examined with the receiver operating characteristic (ROC). RESULTS: The results showed significant differences of p < 0.0001, p < 0.0001, and p = 0.0006 between AD patients and control individuals in GADA, Zn, and ZnT8A serum levels, respectively. No significant difference was observed in the serum concentration of vitamin D between AD patients and control cases (p = 0.2993). The expression level of the BDNF gene in AD patients was different from control cases, but it was not statistically significant (p > 0.05). Moreover, ROC curve analysis disclosed a diagnostic potency for serum levels of GADA, Zn, and ZnT8A for AD with an area under the ROC curve of > 0.7 (p < 0.0001, p < 0.0001, and p = 0.0007, respectively). CONCLUSIONS: The results demonstrated the higher serum levels of GADA and ZnT8A and lower serum concentrations of Zn in the patient group. Therefore, these parameters can be discussed as possibly diagnostic in AD cases.

Investigation of serum levels of orexin-A, transforming growth factor ß, and leptin in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease affecting various inflammatory and nutritional parameters. Therefore, this study aimed to investigate the relationship between the Body Mass Index (BMI) of MS patients and the serum levels of leptin, orexin-A, and Transforming Growth Factor ß (TGF-ß). METHODS: This cross-sectional study included 25 patients suffering from MS and 40 healthy individuals as the case and control groups, respectively. The serum levels of leptin, orexin-A, and TGF-ß were assessed in the participants using the Enzyme-Linked Immunosorbent Assay methods. Moreover, data were analyzed using the descriptive statistical indices, t-test, chi-square test, and linear regression test. RESULTS: According to our results, the participants' mean age was 38.04 ± 7.53 and 40.23 ± 5.88 in the case and control groups, respectively. Also, the groups were not significantly different in gender, age, alcohol consumption, and smoking (p > 0.05). It was found that the mean serum levels of orexin-A and TGF-ß were significantly lower in the MS patients compared to the control group, while the mean serum leptin levels were significantly higher (42.8 vs. 18.9 ng/ml, p < 0.001). Moreover, there was no significant relationship between the BMI of the MS patients and their serum levels of orexin-A, TGF-ß, and leptin (p > 0.05). CONCLUSIONS: In conclusion, we found significantly lower levels of orexin-A and TGF-ß and a significantly higher level of leptin in the MS patients compared to the control group. In addition, there was no significant relationship between the BMI and the serum levels of orexin-A, TGF-ß, and leptin in MS patients.

Exploring potential serum levels of Homocysteine, interleukin-1 beta, and apolipoprotein B 48 as new biomarkers for patients with ischemic stroke.

BACKGROUND: Stroke is the second leading cause of death worldwide with heterogeneous characteristics. The subtypes of stroke are due to different pathophysiological regulations and causes. This study aimed to investigate the correlation of serum levels of apolipoprotein B 48, interleukin-1ß and Homocysteine with BMI in patients with ischemic stroke (IS). METHODS: Over one hundred controls (120) and an equal number of IS patients, including 31 women and 89 men, were recruited to participate in the case-control study conducted at Imam Reza Hospital (Tabriz, Iran) from February 2019 to March 2020. We measured serum levels of apolipoprotein B 48, interleukin-1ß, and Homocysteine. Receiver operating characteristic analysis (ROC) was performed to evaluate the diagnostic value of these indices in patients and control groups. RESULTS: The mean serum levels of apolipoprotein B 48, interleukin-1ß, and Homocysteine, were significantly increased in the experimental group compared to the control group with a p-value of 0.001. The ROC curve analysis showed that the area under the curve for apo B48, IL -1ß, hs-CRP, and Homocysteine serum levels were 0.94, 0.98, 0.99, and 1, respectively. CONCLUSIONS: The results of our current study show that the determination of serum levels of apolipoprotein B 48, interleukin-1ß, and Homocysteine can potentially be used to monitor and diagnose IS patients. However, there was no statistically significant correlation between serum levels of apolipoprotein B 48, interleukin 1ß and Homocysteine and BMI in the patient group. However, there was a statistically significant inverse correlation between serum levels of high-sensitivity C-reactive protein (hs-CRP) and BMI in the patient group.

Molecular mechanisms of sex hormones in the development and progression of Alzheimer's disease.

Alzheimer's disease (AD) is a form of brain disorder characterized by various pathological changes in the brain. Numerous studies have shown that sex hormones are involved in the disease. For instance, progesterone, estrogen, and testosterone are well-known steroid sex hormones that play an essential role in AD pathogenesis. The Gender-dependency of AD is attributed to the effect of these hormones on the brain, which plays a neuroprotective role. In recent years, much research has been performed on the protective role of these hormones against nerve cell damage, which are promising for AD management. Hence, in the current review, we aim to decipher the protective role of steroid hormones in AD. Accordingly, we will discuss their functional mechanisms at the genomic and non-genomic scales.

Targeting autophagy in neurodegenerative diseases: From molecular mechanisms to clinical therapeutics.

Many neurodegenerative diseases are associated with pathological aggregation of proteins in neurons. Autophagy is a natural self-cannibalization process that can act as a powerful mechanism to remove aged and damaged organelles as well as protein aggregates. It has been shown that promoting autophagy can attenuate or delay neurodegeneration by removing protein aggregates. In this paper, we will review the role of autophagy in Alzheimer's disease (AD), Parkinson's Disease (PD), and Huntington's Disease (HD) and discuss opportunities and challenges of targeting autophagy as a potential therapeutic avenue for treatment of these common neurodegenerative diseases.

Evaluation of the Serum Dkk-1, Tenascin-C, Oxidative Stress Markers Levels and Wnt Signaling Pathway Genes Expression in Patients with Alzheimer's Disease.

Early diagnosis of Alzheimer's disease (AD) using potential biomarkers may help with implementing early therapeutic interventions, monitoring, and ultimately disease treatment. The current study aimed to evaluate serum levels of DKK-1, TNC, and oxidative stress markers, as well as analyzing the expression of LRP6, GSK3A, and GSK3B genes in patients with AD. Serum levels of DKK-1, TNC, TOS, TAC, and MDA were measured in 40 AD patients and 40 healthy individuals. Additionally, the relative expressions of LRP6, GSK3A, and GSK3B genes in whole blood were evaluated. Receiver operating characteristic (ROC) analysis was used to investigate the incremental diagnostic value of each factor in the study groups. Mean serum levels of DKK-1, TNC, TOS, TAC, and MDA were significantly higher in the AD group compared to the healthy group (p < 0.001). Moreover, a significant difference was observed in the expression of LRP6 and GSK3A genes (p < 0.001) between patients and healthy groups. However, the expression of GSK3B did not significantly differ between the two groups (p > 0.05). With considerable sensitivity and specificity, ROC analysis demonstrated the diagnostic efficacy of DKK-1 and TNC serum levels in AD within an area under the ROC curve of ≥ 0.98 (p ˂ 0.001). The results showed that evaluating serum levels of DKK-1 and TNC, as well as assessing the expression of LRP6, could be utilized for diagnosis and monitoring of AD patients.

Application of Next-Generation Sequencing in Neurodegenerative Diseases: Opportunities and Challenges.

Genetic factors (gene mutations) lead to various rare and prevalent neurological diseases. Identification of underlying mutations in neurodegenerative diseases is of paramount importance due to the heterogeneous nature of the genome and different clinical manifestations. An early and accurate molecular diagnosis are cardinal for neurodegenerative patients to undergo proper therapeutic regimens. The next-generation sequencing (NGS) method examines up to millions of sequences at a time. As a result, the rare molecular diagnoses, previously presented with "unknown causes", are now possible in a short time. This method generates a large amount of data that can be utilized in patient management. Since each person has a unique genome, the NGS has transformed diagnostic and therapeutic strategies into sequencing and individual genomic mapping. However, this method has disadvantages like other diagnostic methods. Therefore, in this review, we aimed to briefly summarize the NGS method and correlated studies to unravel the genetic causes of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, epilepsy, and MS. Finally, we discuss the NGS challenges and opportunities in neurodegenerative diseases.

Comparison between cerebrospinal fluid and serum levels of myelin-associated glycoprotein, total antioxidant capacity, and 8-hydroxy-2'-deoxyguanosine in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelinated lesions in the brain, the spinal cord, and the optic nerve. It is one of the most common neurological disorders. In this study, serum and cerebrospinal fluid (CSF) levels of total antioxidant capacity (TAC), myelin-associated glycoprotein (MAG), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated to determine their effects on MS. MATERIALS AND METHOD: In this study, 25 serum and cerebrospinal samples from MS patients as a case group and 40 serum and CSF samples from healthy participants as a control group were collected and analyzed. Concentrations of TAC, MAG, and 8-OhdG were determined in the samples using a dedicated kit and relayed using the ELISA device. RESULTS: The mean serum antibody levels of MAG and TAC were higher in the case group than the control group, although the difference in the MAG level was not significant (P > 0.05). However, the mean serum level of -8 OHdG was lower in the case group than the control group. Moreover, the mean levels of the evaluated biomarkers in the CSF samples were higher in the case group than in the control group. Still, the difference was only significant in terms of TAC levels (P < 0.05). Receiver operating characteristics curve analysis showed that the area under the curve was 0.71 and 0.69 for 8-OhdG and TAC serum levels, respectively, and 0.73 for both TAC and CSF levels, which was not significantly different from that in other biomarkers. CONCLUSION: Elevated TAC levels in serum and CSF samples and 8-OhdG in serum samples may be associated with MS pathogenesis. However, further investigation is needed to consider these cases as a follow-up to the therapeutic goals or treatment process.

Evaluation of the Diagnostic and Predictive Value of Serum Levels of ANT1, ATG5, and Parkin in Multiple Sclerosis.

OBJECTIVE: Multiple Sclerosis (MS) is a disease of the central nervous system, which ultimately may lead to various disabilities in patients. No definitive cure has yet been developed for the disease. MRI is the method of choice for imaging MS plaques, which would be useful in disease diagnosis as it becomes progressive. Therefore, this study aimed to investigate the serum levels of ANT1 (adenine nucleotide translocase 1), ATG5 (autophagy-related protein 5), and Parkin in patients with MS, all of which play essential roles in MS pathophysiology, as novel serum biomarkers for early diagnosis of the disease. DESIGN AND METHODS: Forty patients in the early stages of the disease, and 40 healthy individuals were selected as the case and control groups. Upon sampling, the serum levels of the biomarkers were measured. RESULTS: The results indicated that autophagy, mitophagy, and mitochondrial apoptosis were different in the case and control groups. The oxidative stress level evaluation revealed low concertation of total antioxidant status (TAS) in the MS patients, while a partial increase accompanied the malondialdehyde (MDA). No significant correlation was observed between oxidative stress and autophagy or mitophagy factors. CONCLUSION: According to the results obtained from this study, the evaluation of serum levels of ANT1, ATG5, and Parkin could be applied in the diagnosis and follow-up of MS patients.

Psychometric properties of the Persian version of the Patient-Weighted Quality of Life in Epilepsy Inventory-10-P.

BACKGROUND: The purpose of the study was to evaluate psychometric properties of the Persian version of the Patient-Weighted Quality of Life in Epilepsy Inventory-10-P (PV QOLIE-10-P). METHODS: The Persian version was obtained from the original version by standard forward/backward translation. We assessed content validity, construct validity by factor analysis, internal consistency, test-retest reliabilities, criterion validity by calculating Pearson/Spearman correlation to the Persian version of the SF-36 inventory the Persian version of the 36-Item Short Form Health Survey (PV SF-36), and discriminant validity by calculating Pearson/Spearman correlation to demographic features and epilepsy-specific characteristics. RESULTS: One hundred and fifty-five adult patients with epilepsy were enrolled in the study. The 10 items of PV QOLIE-10-P were grouped into two factors: epilepsy effects/role function scale (driving, work, social, memory, physical effect, and mental effect) and mental health scale (energy, depression, seizure worry, and overall quality of life). The Cronbach's alpha value was 0.859. Test-retest analysis revealed statistically significant correlations for total score and the scales (correlation coefficient for total score, epilepsy effects/role function, and mental health were 0.7, 0.66 and 0.7respectively). The Pearson correlation coefficient between total scores of the Persian version of QOLIE10-P and SF-36 was 0.822 (p < 0.001). The PV QOLIE-10-P was able to differentiate patients with marriage, education, job, seizure type, seizure frequency, and antiepileptic treatment. CONCLUSION: The Persian version of QOLIE-10-P is a valid and reliable tool to assess the quality of life of patients with epilepsy in Iran.

Correction to: Interaction of opioid with insulin/IGFs signaling in Alzheimer's disease.

The original version of this article unfortunately contained mistake in the Author Group section. Reza Rahbarghazi's family name was inadvertently spelled as "Rahbarghzi".

Investigation of the miRNA146a and miRNA155 gene expression levels in patients with multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease and the most common neurodegenerative status. MicroRNAs play an important role in macrophage response to inflammatory processes, and alterations in miRNA levels trigger the inactivation of specific T lymphocytes. As a result, these factors can lead to autoimmune diseases such as MS. Therefore, to determine the role of MicroRNA-146a and MicroRNA-155 in MS patients, their expression levels in serum of MS patients were compared with healthy controls. In this study, the expression levels of MicroRNA-146a and MicroRNA-155 in 30 serum samples of MS and healthy patients as a control group. MicroRNA extraction and cDNA synthesis was performed according manufacture protocols. The expression levels of MicroRNAs were evaluated by Real Time-PCR. MicroRNA-146a and MicroRNA-155 levels were increased in patients with MS compared to controls. The results demonstrated that EDSS score are increased with increasing level of MicroRNA-146a and MicroRNA-155. ROC curve analysis showed that the area under curve (AUC) was significant for MicroRNA-146a and MicroRNA-155. Increased expression levels of MicroRNA-146a and MicroRNA-155 may be associated with the pathogenesis of MS disease. If this study is conducted in a larger sample population and the above results can be used to identify patients or control patients who are under medical care.

High Glucose Content Abrogated the Normal Activity of Heat Shock Protein Signaling Pathway in Human Neuroblastoma Cells.

BACKGROUND: Detrimental effects of high glucose content (HGC) were proved in different tissues such as the central nervous system. It seems that diabetic conditions could also alter the functional behavior of stem cells residing in the context of the nervous system. METHODS: The possible effects of 40 and 70 mmol glucose were examined on HSP70 signaling pathways with a specific focus on protein translation, folding values of human neuroblastoma cell line SHSY-5Y after 72 h. Human neuroblastoma cells were exposed to 5, 40 and 70 mmol glucose doses. The transcription level of genes related to HSP70 signaling was also evaluated by PCR array. RESULTS: The data from PCR array showed high glucose especially 70 mmol could potentially modulate the normal function of protein folding, endoplasmic reticulum derived protein folding and synthesis in neuroblastoma cells (p <0.05). CONCLUSIONS: Data showed that high glucose condition makes neuroblastoma cells prone to biochemical insufficiency by affecting the function of HSP70 signaling pathway and protein synthesis.