tellurium and Alzheimer-Disease

Mitochondrial diseases are a group of genetic disorders characterized by dysfunctional mitochondria. Within eukaryotic cells, mitochondria contain their own ribosomes, which synthesize small amounts of proteins, all of which are essential for the biogenesis of the oxidative phosphorylation system. The ribosome is an evolutionarily conserved macromolecular machine in nature both from a structural and functional point of view, universally responsible for the synthesis of proteins. Among the diseases afflicting humans, those of ribosomal origin - either cytoplasmic ribosomes (80S) or mitochondrial ribosomes (70S) - are relevant. These are inherited or acquired diseases most commonly caused by either ribosomal protein haploinsufficiency or defects in ribosome biogenesis. Here we review the scientific literature about the recent advances on changes in mitochondrial ribosomal structural and assembly proteins that are implicated in primary mitochondrial diseases and neurodegenerative disorders, and their possible connection with metalloid pollution and toxicity, with a focus on MRPL44, NAM9 (MNA6) and GEP3 (MTG3), whose lack or defect was associated with resistance to tellurite. Finally, we illustrate the suitability of yeast Saccharomyces cerevisiae (S. cerevisiae) and the nematode Caenorhabditis elegans (C. elegans) as model organisms for studying mitochondrial ribosome dysfunctions including those involved in human diseases.

Topics: Alzheimer Disease; Animals; Caenorhabditis elegans; Humans; Mitochondrial Diseases; Ribosomal Proteins; RNA, Ribosomal; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Tellurium

Alzheimer's disease (AD) is characterized by a distinct pattern of cortical thinning and resultant changes in cognition and function. These result in prominent deficits in cognitive-motor automaticity. The relationship between AD-related cortical thinning and decreased automaticity is not well-understood. We aimed to investigate the relationship between cortical thickness regions-of-interest (ROI) and automaticity and attention allocation in AD using hypothesis-driven and exploratory approaches. We performed an ROI analysis of 46 patients with AD. Data regarding MR images, demographic characteristics, cognitive-motor dual task performance, and cognition were extracted from medical records. Cortical thickness was calculated from MR T1 images using FreeSurfer. Data from the dual task assessment was used to calculate the combined dual task effect (cDTE), a measure of cognitive-motor automaticity, and the modified attention allocation index (mAAI). Four hierarchical multiple linear regression models were conducted regressing cDTE and mAAI separately on (1) hypothesis-generated ROIs and (2) exploratory ROIs. For cDTE, cortical thicknesses explained 20.5% (p = 0.014) and 25.9% (p = 0.002) variability in automaticity in the hypothesized ROI and exploratory models, respectively. The dorsal lateral prefrontal cortex (DLPFC) (β =  - 0.479, p = 0.018) and superior parietal cortex (SPC) (β = 0.467, p = 0.003), and were predictors of automaticity. For mAAI, cortical thicknesses explained 20.7% (p = 0.025) and 28.3% (p = 0.003) variability in attention allocation in the hypothesized ROI and exploratory models, respectively. Thinning of SPC and fusiform gyrus were associated with motor prioritization (β =  - 0.405, p = 0.013 and β =  - 0.632, p = 0.004, respectively), whereas thinning of the DLPFC was associated with cognitive prioritization (β = 0.523, p = 0.022). Cortical thinning in AD was related to cognitive-motor automaticity and task prioritization, particularly in the DLPFC and SPC. This suggests that these regions may play a primary role in automaticity and attentional strategy during dual-tasking.

Topics: Alzheimer Disease; Attention; Cadmium Compounds; Cerebral Cortex; Cerebral Cortical Thinning; Cognition; Humans; Magnetic Resonance Imaging; Quantum Dots; Tellurium

Decreased automaticity is common among individuals with neurodegenerative disease and is often assessed using dual-task (DT) paradigms. However, the best methods for assessing performance changes related to DT demands remain inconclusive.. To investigate the reliability and validity of a novel battery of DT measures (DT Effect-Battery (DTE-B)) encompassing three domains: task-specific interference, task prioritization, and automaticity.. Data for this retrospective cross-sectional study included 125 participants with Parkinson's disease (PD), 127 participants with Alzheimer's disease (AD), and 84 healthy older adults. Reliability analyses were conducted using a subset of each population. DTE-B measures were calculated from single and DT performance on the Timed Up and Go test and a serial subtraction task. Construct validity was evaluated via associations within the DTE-B and with theoretically supported measures as well as known-groups validity analyses.. Good to excellent reliability was found for DTE-B measures of task interference (motor and cognitive DT effects) (ICCs≥.658) and automaticity (combined DT effect (cDTE)) (ICCs≥.938). Evidence for convergent validity was found with associations within the hypothesized constructs. Known-groups validity analyses revealed differences in the DTE-B among the healthy group and PD and AD groups (. This study provides evidence to support the DTE-B as a reliable measure of multiple constructs pertinent to DT performance. The cDTE demonstrated evidence to support its validity as a measure of automaticity. Further investigation of the utility of the DTE-B in both PD and AD, as well as other populations, is warranted.

Topics: Aged; Alzheimer Disease; Cadmium Compounds; Cross-Sectional Studies; Gait; Humans; Neurodegenerative Diseases; Parkinson Disease; Postural Balance; Quantum Dots; Reproducibility of Results; Retrospective Studies; Tellurium; Time and Motion Studies; Walking

Beta-amyloid (Aβ) peptides are the major constituents of senile plaques in the brains of Alzheimer's disease (AD) patients. Aβ monomers (AβMs) can coalesce to form small, soluble oligomers (AβOs), followed by reorganization and assembly into long, thread-like fibrils (AβFs). Recently, soluble AβOs have been regarded as reliable molecular biomarkers for the diagnosis of AD because of their high toxicity for neuronal synapse and high concentration levels in the brains of AD patients. In this work, we reported a label-free, sensitive and selective method for visual and fluorescent detection of AβOs based on the inner filter effect (IFE) of gold nanoparticles (AuNPs) on the fluorescence of CdTe quantum dots (QDs). Specifically, the fluorescence of CdTe QDs was quenched significantly by AuNPs through the IFE. PrP(95-110), an AβOs-specific binding peptide from cellular prion protein, triggered the aggregation and color change of AuNPs suspension; thus, the IFE of AuNPs on the fluorescence of CdTe QDs was weakened and the fluorescence intensity was recovered. However, in the presence of AβOs, the specific interaction of AβOs and PrP(95-110) prevented the absorption of PrP(95-110) onto the surface of AuNPs. As a result, the aggregation of AuNPs was inhibited and the fluorescence intensity of CdTe QDs was quenched again. This label-free method is specific for detection of AβOs but not for AβMs and AβFs. The detection limits were found to be 0.5nM for the visual assay and 0.2nM for the fluorescent detection. We believe that this work would be valuable for many investigations related to AD diagnosis and drug discovery.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Biosensing Techniques; Cadmium Compounds; Fluorescence; Fluorescent Dyes; Gold; Humans; Limit of Detection; Metal Nanoparticles; Peptide Fragments; Quantum Dots; Solubility; Spectrometry, Fluorescence; Tellurium

MicroRNAs (miRNAs) regulate many biological processes by post-translational gene silencing. Analysis of miRNA expression profiles is a reliable method for investigating particular biological processes due to the stability of miRNA and the development of advanced sequencing methods. However, this approach is limited by the broad specificity of miRNAs, which may target several mRNAs.. In this study, we developed a method for comprehensive annotation of miRNA array or deep sequencing data for investigation of cellular biological effects. Using this method, the specific pathways and biological processes involved in Alzheimer's disease were predicted with high correlation in four independent samples. Furthermore, this method was validated for evaluation of cadmium telluride (CdTe) nanomaterial cytotoxicity. As a result, apoptosis pathways were selected as the top pathways associated with CdTe nanoparticle exposure, which is consistent with previous studies.. Our findings contribute to the validation of miRNA microarray or deep sequencing results for early diagnosis of disease and evaluation of the biological safety of new materials and drugs.

Topics: Alzheimer Disease; Cadmium Compounds; High-Throughput Nucleotide Sequencing; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Quantum Dots; Tellurium; Transcriptome

Oxidative stress is implicated, either directly or indirectly, in the pathology of a range of human diseases. As a consequence, the development of efficient antioxidants for medical use has become increasingly important. We have synthesised a range of structurally related organo-sulfur, -selenium and -tellurium agents and demonstrated that a combination of electrochemical methodology, in vitro assays and cell culture tests can be used to rationalise the antioxidant activity of these catalytic agents. Based on its exceptionally low anodic oxidation potential (Epa) and high activity against the representative oxidative stressors tert-butyl hydroperoxide and peroxynitrite, 4,4'-dihydroxydiphenyltelluride is predicted to be a potent antioxidant. This compound exhibits a correspondingly high activity with a remarkably low IC50 value of 20 nM, when tested in PC12 cell culture using a bioassay indicative of the early stages of Alzheimer's disease.

Topics: Alzheimer Disease; Animals; Antioxidants; Catalysis; Hydrogen Peroxide; Hydrogen-Ion Concentration; Metallothionein; Oxidation-Reduction; Oxidative Stress; PC12 Cells; Peroxynitrous Acid; Rats; Selenium; Structure-Activity Relationship; Sulfur; Tellurium; Zinc

The possible role of the abnormal trace element tellurium in the pathogenesis of Alzheimer's disease is examined. Tellurium has been reported to produce cognitive impairment and cerebral lipofuscinosis in rats-changes akin to those seen in Kuf's disease, a condition which shares certain clinical and neuropathological features with Alzheimer's disease. Tellurium can damage mitochondria; defects in mitochondrial energy metabolism may be relevant to the pathogenesis of neurodegenerative disease. The deficiency of selenium, which may act physiologically as an antagonist of tellurium, in the Alzheimer's disease brain would also be in keeping with the hypothesis of tellurium toxicity as a factor in the pathogenesis of Alzheimer's disease.

Topics: Adult; Alzheimer Disease; Animals; Energy Metabolism; Humans; Mitochondria; Models, Biological; Neuronal Ceroid-Lipofuscinoses; Rats; Selenium; Tellurium