共查询到20条相似文献,搜索用时 46 毫秒
1.
Esraa Haj Yelena Losev V. Guru KrishnaKumar Edward Pichinuk Hamutal Engel Avi Raveh Ehud Gazit Daniel Segal 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(7):1565-1575
Background
Alzheimer's disease (AD) is the most common neurodegenerative disorder which is characterized by the deposits of intra-cellular tau protein and extra-cellular amyloid-β (Aβ) peptides in the human brain. Understanding the mechanism of protein aggregation and finding compounds that are capable of inhibiting its aggregation is considered to be highly important for disease therapy.Methods
We used an in vitro High-Throughput Screening for the identification of potent inhibitors of tau aggregation using a proxy model; a highly aggregation-prone hexapeptide fragment 306VQIVYK311 derived from tau. Using ThS fluorescence assay we screened a library of 2401 FDA approved, bio-active and natural compounds in attempt to find molecules which can efficiently modulate tau aggregation.Results
Among the screened compounds, palmatine chloride (PC) alkaloid was able to dramatically reduce the aggregation propensity of PHF6 at sub-molar concentrations. PC was also able to disassemble preformed aggregates of PHF6 and reduce the amyloid content in a dose-dependent manner. Insights obtained from MD simulation showed that PC interacted with the key residues of PHF6 responsible for β-sheet formation, which could likely be the mechanism of inhibition and disassembly. Furthermore, PC could effectively inhibit the aggregation of full-length tau and disassemble preformed aggregates.Conclusions
We found that PC possesses “dual functionality” towards PHF6 and full-length tau, i.e. inhibit their aggregation and disassemble pre-formed fibrils.General significance
The “dual functionality” of PC is valuable as a disease modifying strategy for AD, and other tauopathies, by inhibiting their progress and reducing the effect of fibrils already present in the brain. 相似文献2.
Manuela Leri Reiner Oropesa-Nuñez Claudio Canale Sara Raimondi Sofia Giorgetti Elena Bruzzone Vittorio Bellotti Massimo Stefani Monica Bucciantini 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(6):1432-1442
Background
Many data highlight the benefits of the Mediterranean diet and its main lipid component, extra-virgin olive oil (EVOO). EVOO contains many phenolic compounds that have been found effective against several aging- and lifestyle-related diseases, including neurodegeneration. Oleuropein, a phenolic secoiroid glycoside, is the main polyphenol in the olive oil. It has been reported that the aglycone form of Oleuropein (OleA) interferes in vitro and in vivo with amyloid aggregation of a number of proteins/peptides involved in amyloid, particularly neurodegenerative, diseases avoiding the growth of toxic oligomers and displaying protection against cognitive deterioration.Methods
In this study, we carried out a cellular and biophysical study on the relationships between the effects of OleA on the aggregation and cell interactions of the D76N β2-microglobulin (D76N b2m) variant associated with a familial form of systemic amyloidosis with progressive bowel dysfunction and extensive visceral amyloid deposits.Results
Our results indicate that OleA protection against D76N b2m cytotoxicity results from i) a modification of the conformational and biophysical properties of its amyloid fibrils; ii) a modification of the cell bilayer surface properties of exposed cells.Conclusions
This study reveals that OleA remodels not only D76N b2m aggregates but also the cell membrane interfering with the misfolded proteins-cell membrane association, in most cases an early event triggering amyloid–mediated cytotoxicity.General significance
The data provided in the present article focus on OleA protection, featuring this polyphenol as a promising plant molecule useful against amyloid diseases. 相似文献3.
Anne M. Reiner Felix Schmidt Sergey Ryazanov Andrei Leonov Daniel Weckbecker Andreas A. Deeg Christian Griesinger Armin Giese Wolfgang Zinth 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(4):800-807
Background
Recently diphenyl-pyrazole (DPP) compounds and especially anle138b were found to reduce the aggregation of α-synuclein or Tau protein in vitro as well as in a mouse model of neurodegenerative diseases [1,2]. Direct interaction of the DPPs with the fibrillar structure was identified by fluorescence spectroscopy. Thereby a strong dependence of the fluorescence on the surroundings could be identified [3].Methods
Stationary and time-resolved emission experiments were performed on DPP compounds substituted by different halogens.Results
The compounds reveal a pronounced dependence of the fluorescence on the surrounding solvent. In non-polar solvents they show strong emission in the blue part of the spectrum while in polar and proton donating solvents, such as water or acetic acid a dual fluorescence can be observed where a red-shifted emission points to a charge transfer in the excited state with large dipole moment. Non-radiative processes including photochemical reactions are observed for DPP substituted with heavy halogens. Upon binding of anle138b and its derivatives to protein fibrils in aqueous buffer, strong enhancement of the fluorescence at short wavelengths is found.Conclusion
The investigations of the DPPs in different surroundings lead to a detailed model of the fluorescence characteristics. We propose a model for the binding in fibrils of different proteins, where the DPP is located in a hydrophobic groove independent of the specific sequence of the amino acids.General significance
These investigations characterize the binding site of the DPP anle138b in protein aggregates and contribute to the understanding of the therapeutic mode of action of this compound. 相似文献4.
Andrea Pica Serena Leone Rocco Di Girolamo Federica Donnarumma Alessandro Emendato Michele Fortunato Rega Antonello Merlino Delia Picone 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(4):808-815
Background
MNEI and its variant Y65R-MNEI are sweet proteins with potential applications as sweeteners in food industry. Also, they are often used as model systems for folding and aggregation studies.Methods
X-ray crystallography was used to structurally characterize Y65R-MNEI at five different pHs, while circular dichroism and fluorescence spectroscopy were used to study their thermal and chemical stability. ThT assay and AFM were used for studying the kinetics of aggregation and morphology of the aggregates.Results
Crystal structures of Y65R-MNEI revealed the existence of a dimer in the asymmetric unit, which, depending on the pH, assumes either an open or a closed conformation. The pH dramatically affects kinetics of formation and morphology of the aggregates: both MNEI and Y65R-MNEI form fibrils at acidic pH while amorphous aggregates are observed at neutral pH.Conclusions
The mutation Y65R induces structural modifications at the C-terminal region of the protein, which account for the decreased stability of the mutant when compared to MNEI. Furthermore, the pH-dependent conformation of the Y65R-MNEI dimer may explain the different type of aggregates formed as a function of pH.General significance
The investigation of the structural bases of aggregation gets us closer to the possibility of controlling such process, either by tuning the physicochemical environmental parameters or by site directed mutagenesis. This knowledge is helpful to expand the range of stability of proteins with potential industrial applications, such as MNEI and its mutant Y65R-MNEI, which should ideally preserve their structure and soluble state through a wide array of conditions. 相似文献5.
Shreyasi Asthana Zaved Hazarika Parth Sarathi Nayak Jyoti Roy Anupam Nath Jha Bibekanand Mallick Suman Jha 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):153-166
Background
Injection localized amyloidosis is one of the most prevalent disorders in type II diabetes mellitus (TIIDM) patients relying on insulin injections. Previous studies have reported that nanoparticles can play a role in the amyloidogenic process of proteins. Hence, the present study deals with the effect of zinc oxide nanoparticles (ZnONP) on the amyloidogenicity and cytotoxicity of insulin.Methods
ZnONP is synthesised and characterized using XRD, Zeta Sizer, UV-Visible spectroscope and TEM. The characterization is followed by ZnONP interaction with insulin, which is studied employing fluorescence spectroscopes, isothermal titration calorimetry and molecular dynamics simulations. The interaction leads insulin conformational rearrangement into amyloid-like fibril, which is studied using thioflavin T dye binding assay, circular dichroism spectroscopy and TEM, followed by cytotoxicity propensity using Alamar Blue dye reduction assay.Results
Insulin has very weak interaction with ZnONP interface. Insulin at studied concentration forms amorphous aggregates at physiological pH, whereas in presence of ZnONP interface amyloid-like fibrils are formed. While the amyloid-like fibrils are cytotoxic to MIN6 and THP-1 cell lines, insulin and ZnONP individual solutions and their fresh mixtures enhance the cells proliferation.Conclusions
The presence of ZnONP interface enhances insulin fibrillation at physiological pH by providing a favourable template for the nucleation and growth of insulin amyloids.General significance
The studied protein-nanoparticle system from protein conformational dynamics point of view throws caution over nanoparticle use in biological applications, especially in vivo applications, considering the amyloidosis a very slow but non-curable degenerative disease. 相似文献6.
Rosa Gaglione Giovanni Smaldone Rocco Di Girolamo Renata Piccoli Emilia Pedone Angela Arciello 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):377-384
Background
Specific apolipoprotein A-I variants are associated to severe hereditary amyloidoses. The organ distribution of AApoAI amyloidosis seems to depend on the position of the mutation, since mutations in residues from 1 to 75 are mainly associated to hepatic and renal amyloidosis, while mutations in residues from 173 to 178 are mostly responsible for cardiac, laryngeal, and cutaneous amyloidosis. Molecular bases of this tissue specificity are still poorly understood, but it is increasingly emerging that protein destabilization induced by amyloidogenic mutations is neither necessary nor sufficient for amyloidosis development.Methods
By using a multidisciplinary approach, including circular dichroism, dynamic light scattering, spectrofluorometric and atomic force microscopy analyses, the effect of target cells on the conformation and fibrillogenic pathway of the two AApoAI amyloidogenic variants AApoAIL75P and AApoAIL174S has been monitored.Results
Our data show that specific cell milieus selectively affect conformation, aggregation propensity and fibrillogenesis of the two AApoAI amyloidogenic variants.Conclusions
An intriguing picture emerged indicating that defined cell contexts selectively induce fibrillogenesis of specific AApoAI variants.General significance
An innovative methodological approach, based on the use of whole intact cells to monitor the effects of cell context on AApoAI variants fibrillogenic pathway, has been set up. 相似文献7.
Wataru Yoshida Mizuki Terasaka Saowalak Laddachote Isao Karube 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):1933-1937
Background
DNA methylation at the 5-position of cytosine is an epigenetic modification of CpG dinucleotides. In addition to CpG methylation, the G-quadruplex (G4) structure has been reported as a regulator of gene expression. The identification of G4 forming sequences in CpG islands suggests an involvement of CpG-methylated G4 structures in biological processes; however, few reports have addressed the effects of CpG methylation on G4 structure.Methods
The thermostability of a methylated, 21-mer G4 structure located on the vascular endothelial growth factor (VEGF) gene promoter containing four CpG sites (C1, C6, C11, and C17) were investigated using circular dichroism (CD) spectral analysis.Results
CD melting analysis revealed that VEGF G4 was stabilized by a single CpG methylation on C11 in the presence of Na+ and Mg2+. However, either C1 or C11 methylation enhanced VEGF G4 thermal stability in the presence of K+.Conclusions
Single CpG methylation appears to enhance VEGF G4 thermostability in a manner dependent on both the CpG methylation site and cation type.General significance
These results are expected to contribute to the elucidation of the roles of CpG methylation-stabilized G4 structures in biological processes. 相似文献8.
Dunja Urbančič Anita Kotar Alenka Šmid Marko Jukič Stanislav Gobec Lars-Göran Mårtensson Janez Plavec Irena Mlinarič-Raščan 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):182-190
Background
Methylation driven by thiopurine S-methylatransferase (TPMT) is crucial for deactivation of cytostatic and immunosuppressant thiopurines. Despite its remarkable integration into clinical practice, the endogenous function of TPMT is unknown.Methods
To address the role of TPMT in methylation of selenium compounds, we established the research on saturation transfer difference (STD) and 77Se NMR spectroscopy, fluorescence measurements, as well as computational molecular docking simulations.Results
Using STD NMR spectroscopy and fluorescence measurements of tryptophan residues in TPMT, we determined the binding of selenocysteine (Sec) to human recombinant TPMT. By comparing binding characteristics of Sec in the absence and in the presence of methyl donor, we confirmed S-adenosylmethionine (SAM)-induced conformational changes in TPMT. Molecular docking analysis positioned Sec into the active site of TPMT with orientation relevant for methylation reaction. Se-methylselenocysteine (MeSec), produced in the enzymatic reaction, was detected by 77Se NMR spectroscopy. A direct interaction between Sec and SAM in the active site of rTPMT and the formation of both products, MeSec and S-adenosylhomocysteine, was demonstrated using NMR spectroscopy.Conclusions
The present study provides evidence on in vitro methylation of Sec by rTPMT in a SAM-dependant manner.General significance
Our results suggest novel role of TPMT and demonstrate new insights into enzymatic modifications of the 21st amino acid. 相似文献9.
Shruti Chakraborty Sayak Ganguli Aritra Chowdhury Michael Ibba Rajat Banerjee 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(8):1801-1809
Background
Under oxidative stress cytoplasmic aminoacyl-tRNA synthetase (aaRSs) substrate specificity can be compromised, leading to tRNA mischarging and mistranslation of the proteome. Whether similar processes occur in mitochondria, which are major cellular sources of reactive oxygen species (ROS), is unknown. However, relaxed substrate specificity in yeast mitochondrial phenylalanyl-tRNA synthetase (ScmitPheRS) has been reported to increase tRNA mischarging and blocks mitochondrial biogenesis.Methods
Non-reducing denaturing PAGE, cysteine reactivity studies, MALDI-TOF mass spectrometry, enzyme assay, western blot, growth assay, circular dichroism, dynamic light scattering and fluorescence spectroscopy were used to study the effect of oxidative stress on ScmitPheRS activity.Results
ScmitPheRS is reversibly inactivated under oxidative stress. The targets for oxidative inactivation are two conserved cysteine residues resulting in reversible intra-molecular disulfide bridge formation. Replacement of either conserved cysteine residue increased viability during growth under oxidative stress.Conclusion
Formation of intra-molecular disulfide bridge under oxidative stress hinders the tRNAPhe binding of the enzyme, thus inactivating ScmitPheRS reversibly.General significance
The ScmitPheRS activity is compromised under oxidative stress due to formation of intra-molecular disulfide bridge. The sensitivity of ScmitPheRS to oxidation may provide a protective mechanism against error-prone translation under oxidative stress. 相似文献10.
11.
Loredana Amigoni Cristina Airoldi Antonino Natalello Margherita Romeo Luisa Diomede Paolo Tortora Maria Elena Regonesi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):279-290
Background
We have previously demonstrated the neuroprotective activity of tetracycline on a Spinocerebellar Ataxia 3 nematode model. Here, we present the screening of a small library of tetracycline congeners in order to identify the most effective compound in preventing ataxin-3 aggregation.Methods
We performed the assays on the Josephin Domain as it is directly involved in the onset of fibrillation. We used thioflavin T and solubility assays to spot out the most effective tetracycline congeners; Fourier transform infrared and NMR spectroscopies to characterize their mode of action. We employed an ataxic Caenorhabditis elegans model to evaluate the pharmacological efficacy of tetracycline congeners.Results
Methacycline was identified as the most effective compound. Like tetracycline, methacycline neither significantly affected the aggregation kinetics nor did it change the secondary structures of the final aggregates but increased the solubility of the aggregated species. Saturation transfer NMR experiments demonstrated methacycline capability to only bind the oligomeric species of Josephin Domain. Competition assays also showed that methacycline binds to the Josephin Domain more tightly than tetracycline. The treatment with methacycline induced a significant improvement in motility and locomotion of the transgenic C. elegans without changing its lifespan. The efficacy was distinctly stronger than that of tetracycline. Noteworthy, unlike tetracycline, methacycline was able to retard aging-related decline in motility of even the healthy worms used.Conclusions
The apparent absence of toxic effects displayed by methacycline, along with its stronger efficacy in contrasting expanded ataxin-3 toxicity, makes it a possible candidate for a chronic treatment of the disease. 相似文献12.
Seong-Cheol Park Il Ryong Kim Jin-Young Kim Yongjae Lee Eun-Ji Kim Ji Hyun Jung Young Jun Jung Mi-Kyeong Jang Jung Ro Lee 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2545-2554
Background
It remains an open question whether plant phloem sap proteins are functionally involved in plant defense mechanisms.Methods
The antifungal effects of two profilin proteins from Arabidopsis thaliana, AtPFN1 and AtPFN2, were tested against 11 molds and 4 yeast fungal strains. Fluorescence profiling, biophysical, and biochemical analyses were employed to investigate their antifungal mechanism.Results
Recombinant AtPFN1 and AtPFN2 proteins, expressed in Escherichia coli, inhibited the cell growth of various pathogenic fungal strains at concentrations ranging from 10 to 160?μg/mL. The proteins showed significant intracellular accumulation and cell-binding affinity for fungal cells. Interestingly, the AtPFN proteins could penetrate the fungal cell wall and membrane and act as inhibitors of fungal growth via generation of cellular reactive oxygen species and mitochondrial superoxide. This triggered the AtPFN variant-induced cell apoptosis, resulting in morphological changes in the cells.Conclusion
PFNs may play a critical role as antifungal proteins in the Arabidopsis defense system against fungal pathogen attacks.General significance
The present study indicates that two profilin proteins, AtPFN1 and AtPFN2, can act as natural antimicrobial agents in the plant defense system. 相似文献13.
Yoshito Abe Naoki Odawara Nantanat Aeimhirunkailas Hinako Shibata Naoki Fujisaki Hirofumi Tachibana Tadashi Ueda 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2570-2578
Background
Light chains are abnormally overexpressed from disordered monoclonal B-cells and form amyloid fibrils, which are then deposited on the affected organ, leading to a form of systemic amyloidosis known as AL (Amyloid Light chain) amyloidosis. A green tea catechin, epigallocatechin-3-O-gallate (EGCG), which is thought to inhibit various amyloidoses, is a potent inhibitor of amyloid fibril formation in AL amyloidosis.Methods
An amyloidogenic variable domain in λ6 light chain mutant, Wil was incubated in the presence of EGCG. The incubation products were analyzed by SDS-PAGE and reverse-phase HPLC. The interaction between Wil and EGCG was observed by using NMR and tryptophan fluorescence.Results
EGCG inhibited the amyloid fibril formation of Wil at pH?7.5 and 42?°C. Under these conditions, most Wil populations were in the unfolded state and several chemical reactions, i.e., oxidation and/or covalent bond oligomerization could be induced by auto-oxidated EGCG. Moreover, we found that EGCG bound to the unfolded state of Wil with higher affinity (Kd?=?7?μM).Conclusions
Inhibition of amyloid fibril formation of Wil was caused by 1) EGCG binding to unfolded state rather than folded state and 2) chemical modifications of Wil by auto oxidation of EGCG.General significance
In the competitive formation of amyloid fibrils and off-pathway oligomers, EGCG produces the latter immediately after it preferentially binds to the unfolded state. It may be general mechanism of EGCG inhibition for amyloidosis. 相似文献14.
Rani Kunjithapatham Shanmugasundaram Ganapathy-Kanniappan 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2555-2563
Background
Rapid utilization of glucose is a metabolic signature of majority of cancers, hence enzymes of the glycolytic pathway remain attractive therapeutic targets. Recent reports have shown that targeting the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an abundant, ubiquitous multifunctional protein frequently upregulated in cancer, affects cancer progression. Here, we report that a catalytically-deficient mutant-GAPDH competitively inhibits the wild-type, and disrupts glucose metabolism in cancer cells.Methods
Using site-directed mutagenesis, the human GAPDH clone was mutated at one of the NAD+-binding sites, (i.e.) arginine (R13) and isoleucine (I14) to glutamine (Q13) and phenylalanine (F14), respectively. The inhibitory role of the mutant-GAPDH, and its effect on energy metabolism and cancer phenotype was determined using in vitro and in vivo models of cancer.Results
The enzymatically-dysfunctional mutant-GAPDH competitively inhibited the wild-type GAPDH in a cell-free system. In cancer cells, ectopic expression of the mutant-GAPDH, but not the wild-type, inhibited the glycolytic capacity of cellular-GAPDH, and led to the induction of metabolic stress accompanied by a sharp decline in glucose-uptake. Furthermore, expression of mutant-GAPDH affected cancer growth in vitro and in vivo. Mechanistically, structural analysis by bioinformatics revealed that the mutations at the NAD+-binding site altered the solvent-accessibility that perhaps affected the functionality of mutant-GAPDH.Conclusion
Mutant-GAPDH affects the enzymatic function of cellular-GAPDH and disrupts energy metabolism.General significance
Our findings demonstrate that a minimal mutation at the NAD+-binding site is sufficient to generate a competitive but dysfunctional GAPDH, and its ectopic expression inhibits the wild-type to disrupt glycolysis. 相似文献15.
Brunna Xavier Martins Raul Ferraz Arruda Gildeíde Aparecida Costa Hassan Jerdy Sávio Bastos de Souza Julianna Maria Santos William Rodrigues de Freitas Milton Masahiko Kanashiro Eulógio Carlos Queiroz de Carvalho Nadir Francisca SantAnna Fernanda Antunes Raul Martinez-Zaguilan Sennoune Souad Anna Lvovna Okorokova-Fa?anha Arnoldo Rocha Fa?anha 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):1-12
Background
Metastatic tumor cells have acidic extracellular pH and differential electrochemical H+ gradients generated across their cell membranes by V-type H+-ATPases. This study shows that inhibition of the V-ATPases by the plant-derived monoterpene Myrtenal results in tumor cell death and decreased metastatic dissemination in mice.Methods
The Myrtenal anticancer toxicity was evaluated in vitro using murine (B16F0 and B16F10) and human (SkMel-5) melanoma cell lines, and in in vivo mouse metastatic dissemination model. Proton flux and extracellular acidification were directly evaluated at the surface of living cells using a non-invasive selective ion electrode approach.Results
The inhibition of V-ATPases by 100?μM Myrtenal disrupted the electrochemical H+ gradient across the cell membranes, strongly induced cell death (4–5 fold), and decreased tumor cells migration and invasion in vitro. Myrtenal (15?mg/kg) also significantly reduced metastasis induced by B16F10 in vivo, further reinforcing that V-ATPase is a molecular target to halt the progression of cancers.Conclusions
These data revealed the therapeutic potential of Myrtenal as inhibitor of melanoma progression proposing a mechanism of action by which once inhibited by this monoterpene the proton pumps fail to activate cancer-related differential electrochemical gradients and H+ fluxes across the tumor cell membranes, disrupting pH signatures inherent in tumor progression, resulting in reprogrammed cell death and metastasis inhibition.General significance
The work represents a new mechanistic strategy for contention of melanoma, the most aggressive and deadly form of cutaneous neoplasm, and highlights Myrtenal, other related monoterpenes and derivatives as promising proton pump inhibitors with high chemotherapeutic potential. 相似文献16.
17.
Joel Tellinghuisen 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(4):886-894
Background
Questions about the reliability of parametric standard errors (SEs) from nonlinear least squares (LS) algorithms have led to a general mistrust of these precision estimators that is often unwarranted.Methods
The importance of non-Gaussian parameter distributions is illustrated by converting linear models to nonlinear by substituting eA, ln A, and 1/A for a linear parameter a. Monte Carlo (MC) simulations characterize parameter distributions in more complex cases, including when data have varying uncertainty and should be weighted, but weights are neglected. This situation leads to loss of precision and erroneous parametric SEs, as is illustrated for the Lineweaver-Burk analysis of enzyme kinetics data and the analysis of isothermal titration calorimetry data.Results
Non-Gaussian parameter distributions are generally asymmetric and biased. However, when the parametric SE is < 10% of the magnitude of the parameter, both the bias and the asymmetry can usually be ignored. Sometimes nonlinear estimators can be redefined to give more normal distributions and better convergence properties.Conclusion
Variable data uncertainty, or heteroscedasticity, can sometimes be handled by data transforms but more generally requires weighted LS, which in turn require knowledge of the data variance.General significance
Parametric SEs are rigorously correct in linear LS under the usual assumptions, and are a trustworthy approximation in nonlinear LS provided they are sufficiently small — a condition favored by the abundant, precise data routinely collected in many modern instrumental methods. 相似文献18.
Yue Liu James Clement Ross Grant Perminder Sachdev Nady Braidy 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2527-2532
Background
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is currently investigated as an important target to extend lifespan and health span. Age-related NAD+ depletion due to the accumulation of oxidative stress is associated with reduced energy production, impaired DNA repair and genomic instability.Scope of review
NAD+ levels can be elevated therapeutically using NAD+ precursors or through lifestyle modifications including exercise and caloric restriction. However, high amounts of NAD+ may be detrimental in cancer progression and may have deleterious immunogenic roles.Major conclusions
Standardized quantitation of NAD+ and related metabolites may therefore represent an important component of NAD+ therapy.General significance
Quantitation of NAD+ may serve dual roles not only as an ageing biomarker, but also as a diagnostic tool for the prevention of malignant disorders. 相似文献19.
Sophie Debs Amy Cohen Elham Hosseini-Beheshti Giovanna Chimini Nicholas H. Hunt Georges E.R. Grau 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):325-331
Background
Malaria is a serious parasitic infection affecting millions of people worldwide each year. Cerebral malaria is the most severe complication of Plasmodium infections, predominantly affecting children. Extracellular vesicles are essential mediators of intercellular communication and include apoptotic bodies, microvesicles and exosomes. Microvesicle numbers increase during disease pathogenesis and inhibition of their release can prevent brain pathology and mortality.Scope of review
We explore the current knowledge on microvesicles and exosomes in cerebral malaria pathogenesis.Major conclusions
Microvesicles and exosomes are implicated in cerebral malaria pathogenesis, in the modulation of host immunity to Plasmodium, and in cell-cell communication. Blocking their production is protective in models of cerebral malaria, both in vivo and in vitro.General significance
While anti-malarial treatments exist to combat Plasmodium infections, increasing drug resistance presents a major challenge. In order to improve diagnosis and treatment outcomes, further research is required to better appreciate extracellular vesicle involvement in cerebral malaria. 相似文献20.
Stephanie Kaypee Smitha Asoka Sahadevan Deepthi Sudarshan Sarmistha Halder Sinha Shilpa Patil Parijat Senapati Gopinath S. Kodaganur Azeem Mohiyuddin Dipak Dasgupta Tapas K. Kundu 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(8):1729-1741