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61.
Seema Jagota Jayakumar Rajadas 《International journal of peptide research and therapeutics》2012,18(1):53-61
Genetic, biochemical and pathological evidence support that self-assembly of amyloid-beta (Aβ) peptide into toxic aggregates
is implicated as the cause of Alzheimer’s disease. An attractive therapeutic strategy for the treatment of AD is to prevent
or interfere with Aβ aggregation. A systematic investigation of the effects of proline-, glycine-, arginine- and lysine- containing
peptides (PGKLVYA, KKLVFFARRRRA and KKLVFFA) on the beta-amyloid aggregation was made using FTIR, circular dichroism, ANS
binding, ThT binding and TEM analysis. These peptides are based on the central hydrophobic region of Aβ (residues 16–20),
which is believed to be crucial in Aβ self-association. There is increasing evidence to suggest that protein aggregation,
including amyloid fibril formation results from the strong self-association tendency of the partially folded intermediates.
Addition of PGKLVYA and KKLVFFARRRRA resulted in increase in ANS fluorescence intensity, suggesting enhanced exposure of hydrophobic
surface area. As observed by ThT and TEM analysis PGKLVYA and KKLVFFARRRRA promote non-fibrillar ensembles, while peptide
KKLVFFA accelerated the fibrillization of Aβ peptide by stabilizing intermolecular interactions. Circular dichroism and FTIR
data showed that PGKLVYA and KKLVFFARRRRA effectively prevented amyloid-beta (Aβ) peptide adopting the beta-sheet secondary
structure correlated with fibrillogenesis. This result indicates that PGKLVYA and KKLVFFARRRRA might have triggered another
mechanism of Aβ assembly. 相似文献
62.
63.
Tao Yang Juliet K. Knowles Qun Lu Hong Zhang Ottavio Arancio Laura A. Moore Timothy Chang Qian Wang Katrin Andreasson Jayakumar Rajadas Gerald G. Fuller Youmei Xie Stephen M. Massa Frank M. Longo 《PloS one》2008,3(11)
The p75 neurotrophin receptor (p75NTR) is expressed by neurons particularly vulnerable in Alzheimer''s disease (AD). We tested the hypothesis that non-peptide, small molecule p75NTR ligands found to promote survival signaling might prevent Aβ-induced degeneration and synaptic dysfunction. These ligands inhibited Aβ-induced neuritic dystrophy, death of cultured neurons and Aβ-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Aβ-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3β and c-Jun, and tau phosphorylation, and prevented Aβ-induced inactivation of AKT and CREB. Finally, a p75NTR ligand blocked Aβ-induced hippocampal LTP impairment. These studies support an extensive intersection between p75NTR signaling and Aβ pathogenic mechanisms, and introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling pathways, reverse synaptic impairment and inhibit Aβ-induced neuronal dystrophy and death. 相似文献
64.
Jesudason EP Masilamoni JG Ashok BS Baben B Arul V Jesudoss KS Jebaraj WC Dhandayuthapani S Vignesh S Jayakumar R 《Molecular and cellular biochemistry》2008,311(1-2):145-156
Aβ amyloid peptide is believed to induce oxidative stress leading to inflammation, which is postulated to play a significant
role in the toxicity of Alzheimer’s disease (AD). This study was designed to investigate the inhibitory effects of dl-α lipoic acid (LA), a potential free radical scavenger, on oxidative vulnerability induced by intraperitoneal injection of
Aβ25–35 amyloid fibrils in mice. Mice were divided into three groups: control, Aβ amyloid toxicity induced (AT), and LA treated (ATL).
Blood Plasma was separated, liver, spleen and brain were dissected and analysis of oxidants, antioxidants, ATPases, glial
fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NFκB) were carried out. Results show biochemical parameters such
as reactive oxygen species (ROS) and lipid peroxidation (LPO) were significantly lowered (P < 0.05) and levels of antioxidants and ATPase (P < 0.05) were significantly increased (P < 0.05) in hepatocytes, splenocytes and astrocytes of the ATL group. Moreover, our histological results revealed a decreased
GFAP immunoreactivity in the neocortical region and NFκB immunoreactivity in neocortex, liver and spleen. This study reiterates
LA as a potent free radical scavenger to combat oxidative vulnerability in the treatment for Aβ amyloid toxicity. 相似文献
65.
Sambasivam D Liu CW Jayaraman M Malar EJ Rajadas J 《Biochimica et biophysica acta》2008,1784(11):1659-1667
Most of the disease causing proteins such as beta amyloid, amylin, and huntingtin protein, which are natively disordered, readily form fibrils consisting of beta-sheet polymers. Though all amyloid fibrils are made up of beta-sheet polymers, not all peptides with predominant beta-sheet content in the native state develop into amyloid fibrils. We hypothesize that stable amyloid like fibril formation may require mixture of different conformational states in the peptide. We have tested this hypothesis on amyloid forming peptide namely HCl(Ile)(5)NH(CH(2)CH(2)O)(3)CH(3) (I). We show peptide I, has propensity to form self-assembled structures of beta-sheets in aqueous solutions. When incubated over a period of time in aqueous buffer, I self assembled into beta sheet like structures with diameters ranging from 30 to 60 A that bind with amyloidophilic dyes like Congo red and Thioflavin T. Interestingly peptide I developed into unstable fibrils after prolonged aging at higher concentration in contrast with the general mature fibril-forming propensity of various amyloid petides known to date. 相似文献
66.
67.
S. Raj V. Vinod J. Jayakumar P. Suresh A. Kumar R. Biswas 《Letters in applied microbiology》2021,73(1):31-38
Candida species are opportunistic human fungal pathogens that cause acute and chronic infections against which only few antifungal agents are available. Here we have elucidated the antifungal effect of Syzygium samarangense leaf extracts (SSLE). Antifungal activity of SSLE was studied against Candida albicans, C. krusei, C. parapsilosis, C. glabrata, C. auris and C. tropicalis. Following experiments were performed: minimum fungicidal concentration (MFC) determination, agar well disc diffusion assays, fungal morphology analysis using scanning electron microscope (SEM), ex vivo fungal survival assays on porcine tongue and skin and in vivo fungal survival assays using Drosophila melanogaster fly model. Results demonstrated MFC of SSLE ranges between 100 and 125 mg ml−1. SEM images showed cell wall degradation of C. albicans when treated with SSLE. Around 75% decrease in C. albicans viability was observed when infected porcine tongue and skin were treated using SSLE. The C. albicans infected D. melanogaster when fed with SSLE showed significant decrease (around 80%) of fungal count than the infected control. Furthermore, agar plate disc diffusion assays demonstrated that the antifungal activity of SSLE could be due to chalcone, which is one of the active constituents in SSLE. Our study demonstrated that SSLE could be used for the topical treatment of Candida infections. 相似文献
68.
K. Parthasarathy C. Praveen C. Balachandran P. Senthil kumar S. Ignacimuthu P.T. Perumal 《Bioorganic & medicinal chemistry letters》2013,23(9):2708-2713
Cu(OTf)2 catalyzed efficient synthesis of spiropyrano[3,2-b]pyran-4(8H)-ones is accomplished via one-pot three component reaction between isatin, kojic acid and active methylenes. This synthetic protocol is operationally simple and affords product with good to excellent yields at a short reaction time. The synthesized compounds were evaluated for their tumor cell growth inhibitory activity against the human lung cancer cell line (A549) and found that 13 compounds exhibited moderate to good anticancer potency. Molecular docking studies were performed for all the synthesized compounds and the results showed that compound 4e showed greater affinity for anaplastic lymphoma kinase (ALK) receptor. 相似文献
69.
Ayyasami Ramanathan Perumal Vidhyasekaran Luke Rathinakumar 《Archives Of Phytopathology And Plant Protection》2013,46(2):105-114
Several regenerants through organogenesis were obtained in greengram ( Vigna radiata L. wilczek). Cytokinins appear to be important in inducing organogenesis and IAA induces root induction. Heritable variations could be seen among organogenesis regenerants. Some of the regenerants showed resistance to powdery mildew while some others showed resistance to yellow mosaic virus disease. The disease resistant characters were stable also in R 3 and R 4 generations. 相似文献
70.
Ayyanna Repally Venkatesh Perumal Ankaiah Dasari Esakkiraj Palanichamy Arul Venkatesan 《Probiotics and antimicrobial proteins》2018,10(4):775-786
Lactobacillus mucosae strain AN1 isolated from sheep milk and characterized for its probiotic suitability. In vitro evaluation of critical gut endurance properties of this strain were assessed by different screening methods such as bile salt, gastric acid, lysozyme tolerance assays, hemolytic, cholesterol reduction properties, and HT-29 cell line adhesion assay. Antibacterial peptide from this strain was purified using ammonium sulphate precipitation, gel filtration chromatography and reverse-phase HPLC. The molecular mass of peptides was determined by Tricine-SDS-PAGE and confirmed by matrix-assisted laser desorption ionization-time of flight mass spectroscopy (MALDI-TOF-MS). Purified peptide was named as AN1 having a molecular mass of 10.66 kDa. Helical structures of peptide were determined using circular dichroism spectroscopy. Stability of peptide AN1 towards different parameters such as pH, temperature, organic solvents, proteolytic, and glycolytic enzymes was also analyzed. 相似文献