The Role of Astaxanthin on Transcriptional Regulation of NMDA Receptors Voltage Sensitive Calcium Channels and Calcium Binding Proteins in Primary Cortical Neurons

Introduction: Calcium (Ca) is the phenomenon intracellular molecule that regulate many cellular process in neurons physiologically. Calcium dysregulation may occur in neurons due to excessive synaptic release of glutamate or other reasons related with neurodegeneration. Astaxanthin is a carotenoid that has antioxidant effect in cell. The purpose of this study was to investigate whether astaxanthin affects NMDA subunits, calcium binding proteins and L Type voltage sensitive Ca-channels (LVSCC) in primary cortical neuron cultures in order to see its role in calcium metabolism

Vitamin D Receptor Regulates Amyloid Beta 1–42 Production with Protein Disulfide Isomerase A3

The challenge of understanding the biology of neuronal amyloid processing could provide a basis for understanding the amyloid pathology in Alzheimer’s disease (AD). Based on our previous studies, we have suggested that AD might be the consequence of a hormonal imbalance in which the critical hormone is vitamin D. The present study primarily focused on the creation of a condition that prevents the genomic or nongenomic action of vitamin D by disrupting vitamin D receptors (VDR or PDIA3/1,25MARRS); the effects of these disruptions on the series of proteins involved in secretases that play a crucial role in amyloid pathology and on amyloid beta (Aβ) production in primary cortical neurons were observed. VDR and PDIA3/1,25MARRS genes were silenced separately or simultaneously in E16 primary rat cortical neurons. The expression of target genes involved in APP processing, including Presenilin1, Presenilin2, Nicastrin, BACE1, ADAM10, and APP, was investigated with qRT-PCR and Western blot in this model. 1,25-Dihydroxyvitamin D₃ treatments were used to verify any transcriptional regulation data gathered from siRNA treatments by determining the mRNA expression of the target genes. Immunofluorescence labeling was used for the verification of silencing experiments and intracellular Aβ1–42 production. Extracellular Aβ1–42 level was assessed with ELISA. mRNA and protein expression results showed that 1,25-dihydroxyvitamin D₃ might affect the transcriptional regulation of the genes involved in APP processing. The intracellular and extracellular Aβ1–42 measurements in our study support this suggestion. Consequently, we suggest that 1,25-dihydroxyvitamin D₃ and its receptors are important parts of the amyloid processing pathway in neurons

BDNF, TNF alpha, HSP90, CFH, and IL-10 Serum Levels in Patients with Early or Late Onset Alzheimer's Disease or Mild Cognitive Impairment

Identifying early-detection biomarkers have become an increasingly important approach in the treatment and prevention of Alzheimer's disease (AD). In this study, we investigated the potential of brain-derived neurotrophic factor (BDNF), complement factor H(CFH), tumor necrosis factor-alpha (TNF alpha), interleukin 10 (IL-10), and heat shock protein 90 (Hsp90) as serum biomarkers for AD in a cohort of the Turkish population because they have been suggested to be associated with AD. Serum BDNF, CFH, TNF alpha, IL-10, and Hsp90 levels in three groups of patients, early-onset AD (EOAD; age of onset 65; n = 54), and mild cognitive impairment (MCI) (n = 30), were compared with age-matched healthy controls (age 65; n = 32) using ELISA. The serum BDNF levels significantly decreased and TNF alpha levels significantly increased in the EOAD and LOAD groups compared to the age-matched healthy controls. There was a correlation between serum TNF alpha and IL-10 levels in the LOAD and healthy control groups. Serum CFH levels in the LOAD and MCI patients were significantly decreased compared with controls. Serum Hsp90 levels in the EOAD, LOAD, and MCI patients were significantly decreased compared with controls. The protein misfolding, the inflammatory response, and decreased neurotrophic factor synthesis are all suggested to be related to AD type brain pathology, and our results indicate these alterations might be traced from serum samples. For accurate early diagnosis of AD, it is important to determine a profile of alterations in multiple biomarkers in large-scale population studies

BDNF, TNFα, HSP90, CFH, and IL-10 Serum Levels in Patients with Early or Late Onset Alzheimer's Disease or Mild Cognitive Impairment

Identifying early-detection biomarkers have become an increasingly important approach in the treatment and prevention of Alzheimer's disease (AD). In this study, we investigated the potential of brain-derived neurotrophic factor (BDNF), complement factor H(CFH), tumor necrosis factor-alpha (TNF alpha), interleukin 10 (IL-10), and heat shock protein 90 (Hsp90) as serum biomarkers for AD in a cohort of the Turkish population because they have been suggested to be associated with AD. Serum BDNF, CFH, TNF alpha, IL-10, and Hsp90 levels in three groups of patients, early-onset AD (EOAD; age of onset 65; n = 54), and mild cognitive impairment (MCI) (n = 30), were compared with age-matched healthy controls (age 65; n = 32) using ELISA. The serum BDNF levels significantly decreased and TNF alpha levels significantly increased in the EOAD and LOAD groups compared to the age-matched healthy controls. There was a correlation between serum TNF alpha and IL-10 levels in the LOAD and healthy control groups. Serum CFH levels in the LOAD and MCI patients were significantly decreased compared with controls. Serum Hsp90 levels in the EOAD, LOAD, and MCI patients were significantly decreased compared with controls. The protein misfolding, the inflammatory response, and decreased neurotrophic factor synthesis are all suggested to be related to AD type brain pathology, and our results indicate these alterations might be traced from serum samples. For accurate early diagnosis of AD, it is important to determine a profile of alterations in multiple biomarkers in large-scale population studies

Vitamin D deficiency might pose a greater risk for ApoEɛ4 non-carrier Alzheimer’s disease patients

© 2016, Springer-Verlag Italia.Vitamin D is a secosteroid hormone that shares a synthetic pathway with cholesterol. ApoE, which is involved in the transport of cholesterol, is the most significant genetic risk factor for sporadic Alzheimer’s disease (AD). Surprisingly, recent studies have indicated the presence of an evolutionary juncture between these two molecules. To demonstrate this possible relationship, we investigated serum levels of 25-hydroxyvitamin-D3 (25OHD) in patients with early onset-AD (EOAD; n:22), late onset-AD (LOAD; n:72), mild cognitive impairment (MCI; n:32) and in healthy subjects (n:70). We then analyzed the correlation between 25OHD and cytokines, BDNF and Hsp90 with respect to ApoE alleles, as these molecules were investigated in our previous studies. The LOAD patients had low levels of 25OHD, but these low levels originated only from ApoEɛ4 non-carrier patients. Negative correlations were observed between serum 25OHD and TNFα, IL-1β or IL-6 levels in healthy subjects or MCI patients, but these same correlations were positive in LOAD patients. ApoE alleles indicated that these positive correlations exist only in ɛ4 carrier LOAD patients. Consequently, our results indicate that vitamin D deficiency presents a greater risk for ApoEɛ4 non-carrier AD patients than for ɛ4 carriers. Therefore, it might be beneficial to monitor the vitamin D status of ApoEɛ4 allele non-carrier AD patients

GC and VDR SNPs and Vitamin D Levels in Parkinson's Disease: The Relevance to Clinical Features

Vitamin D deficiency is suggested to be associated with Parkinson's disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D-3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hundred eighty-two PD patients and 242 healthy subjects were included in this study. The serum 25OHD levels were investigated by CLIA, and GC and VDR SNPs were evaluated with LightSnip. Our results indicated a strong relationship between low serum 25OHD levels and PD (p < 0.001). rs7041 of GC and ApaI of VDR were associated with the PD risk (p < 0.05). Minor allele carriers for BsmI of VDR gene in both PD patients and healthy subjects had significantly higher levels of serum 25OHD (p < 0.05). The homozygous major allele carriers for rs2282679, rs3755967 and rs2298850 of GC gene in PD patients with slower progression had significantly higher levels of serum 25OHD (p < 0.05). Minor allele carriers for FokI of VDR gene were more frequent in patients with advanced-stage PD (p < 0.05). Consequently, this is the first study demonstrating GC gene as a risk factor for PD. The relationship between PD's clinical features and low 25OHD or risk genotypes might have effects on PD independently

The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer's disease, mild cognitive impairment or Parkinson's disease

© 2015 Elsevier B.V.Alzheimer's disease (EOAD, LOAD), mild cognitive impairment (MCI), Parkinson's disease (PD) and healthy controls were included to determine the serum interleukin-1s (IL-1α, IL-1β), IL-6 and alpha-2-macroglobulin (α2M) levels using ELISA.IL-6 might be a significant contributor to the inflammatory response in LOAD. The MCI data indicate that IL-1s, α2M and BDNF are somehow related, and this relationship might allow MCI patients to be more similar to the healthy controls.A correlation analysis of multiple biomarkers in different neurodegenerative disorders might be more useful than determining the levels of a single cytokine in a single disorder