Displaying publications 1 - 20 of 107 in total

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  1. A Protein Decomplexation Strategy in Snake Venom Proteomics
    Tan CH, Tan KY, Tan NH
    Methods Mol Biol, 2019;1871:83-92.
    PMID: 30276733 DOI: 10.1007/978-1-4939-8814-3_5
    Snake venoms are complex mixtures of proteins and peptides that play vital roles in the survival of venomous snakes. As with their diverse pharmacological activities, snake venoms can be highly variable, hence the importance of understanding the compositional details of different snake venoms. However, profiling venom protein mixtures is challenging, in particular when dealing with the diversity of protein subtypes and their abundances. Here we described an optimized strategy combining a protein decomplexation method with in-solution trypsin digestion and mass spectrometry of snake venom proteins. The approach involves the integrated use of C18 reverse-phase high-performance liquid chromatography (RP-HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and nano-electrospray ionization tandem mass spectrometry (nano-ESI-LC-MS/MS).
    Matched MeSH terms: Peptides/metabolism
  2. Fulltext A Review on the Relationship between Tocotrienol and Alzheimer Disease
    Chin KY, Tay SS
    Nutrients, 2018 Jul 09;10(7).
    PMID: 29987193 DOI: 10.3390/nu10070881
    Alzheimer’s disease (AD) is plaguing the aging population worldwide due to its tremendous health care and socioeconomic burden. Current treatment of AD only offers symptomatic relief to patients. Development of agents targeting specific pathologies of AD is very slow. Tocotrienol, a member of the vitamin E family, can tackle many aspects of AD, such as oxidative stress, mitochondrial dysfunction and abnormal cholesterol synthesis. This review summarizes the current evidence on the role of tocotrienol as a neuroprotective agent. Preclinical studies showed that tocotrienol could reduce oxidative stress by acting as a free-radical scavenger and promoter of mitochondrial function and cellular repair. It also prevented glutamate-induced neurotoxicity in the cells. Human epidemiological studies showed a significant inverse relationship between tocotrienol levels and the occurrence of AD. However, there is no clinical trial to support the claim that tocotrienol can delay or prevent the onset of AD. As a conclusion, tocotrienol has the potential to be developed as an AD-preventing agent but further studies are required to validate its efficacy in humans.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  3. A critical role of TRPM2 channel in Aβ42 -induced microglial activation and generation of tumor necrosis factor-α
    Alawieyah Syed Mortadza S, Sim JA, Neubrand VE, Jiang LH
    Glia, 2018 03;66(3):562-575.
    PMID: 29143372 DOI: 10.1002/glia.23265
    Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD. Exposure to 10-300 nM Aβ42 induced concentration-dependent microglial activation and generation of TNF-α that were ablated by genetically deleting (TRPM2 knockout ;TRPM2-KO) or pharmacologically inhibiting the TRPM2 channel, revealing a critical role of this channel in Aβ42 -induced microglial activation and generation of TNF-α. Mechanistically, Aβ42 activated the TRPM2 channel via stimulating generation of reactive oxygen species (ROS) and activation of poly(ADPR) polymerase-1 (PARP-1). Aβ42 -induced generation of ROS and activation of PARP-1 and TRPM2 channel were suppressed by inhibiting protein kinase C (PKC) and NADPH oxidases (NOX). Aβ42 -induced activation of PARP-1 and TRPM2 channel was also reduced by inhibiting PYK2 and MEK/ERK. Aβ42 -induced activation of PARP-1 was attenuated by TRPM2-KO and moreover, the remaining PARP-1 activity was eliminated by inhibiting PKC and NOX, but not PYK2 and MEK/ERK. Collectively, our results suggest that PKC/NOX-mediated generation of ROS and subsequent activation of PARP-1 play a role in Aβ42 -induced TRPM2 channel activation and TRPM2-dependent activation of the PYK2/MEK/ERK signalling pathway acts as a positive feedback to further facilitate activation of PARP-1 and TRPM2 channel. These findings provide novel insights into the mechanisms underlying Aβ-induced AD-related neuroinflammation.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism*
  4. A reappraisal on amyloid cascade hypothesis: the role of chronic infection in Alzheimer's disease
    Phuna ZX, Madhavan P
    Int J Neurosci, 2023 Dec;133(10):1071-1089.
    PMID: 35282779 DOI: 10.1080/00207454.2022.2045290
    Alzheimer disease (AD) is a progressive neurological disorder that accounted for the most common cause of dementia in the elderly population. Lately, 'infection hypothesis' has been proposed where the infection of microbes can lead to the pathogenesis of AD. Among different types of microbes, human immunodeficiency virus-1 (HIV-1), herpes simplex virus-1 (HSV-1), Chlamydia pneumonia, Spirochetes and Candida albicans are frequently detected in the brain of AD patients. Amyloid-beta protein has demonstrated to exhibit antimicrobial properties upon encountering these pathogens. It can bind to microglial cells and astrocytes to activate immune response and neuroinflammation. Nevertheless, HIV-1 and HSV-1 can develop into latency whereas Chlamydia pneumonia, Spirochetes and Candida albicans can cause chronic infections. At this stage, the DNA of microbes remains undetectable yet active. This can act as the prolonged pathogenic stimulus that over-triggers the expression of Aβ-related genes, which subsequently lead to overproduction and deposition of Aβ plaque. This review will highlight the pathogenesis of each of the stated microbial infection, their association in AD pathogenesis as well as the effect of chronic infection in AD progression. Potential therapies for AD by modulating the microbiome have also been suggested. This review will aid in understanding the infectious manifestations of AD.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  5. Aberrant proteins in the saliva of patients with oral squamous cell carcinoma
    Jessie K, Jayapalan JJ, Ong KC, Abdul Rahim ZH, Zain RM, Wong KT, et al.
    Electrophoresis, 2013 Sep;34(17):2495-502.
    PMID: 23784731 DOI: 10.1002/elps.201300107
    Confirmation of oral squamous cell cancer (OSCC) currently relies on histological analysis, which does not provide clear indication of cancer development from precancerous lesions. In the present study, whole saliva proteins of patients with OSCC (n = 12) and healthy subjects (n = 12) were separated by 2DE to identify potential candidate biomarkers that are much needed to improve detection of the cancer. The OSCC patients' 2DE saliva protein profiles appeared unique and different from those obtained from the healthy subjects. The patients' saliva α1-antitrypsin (AAT) and haptoglobin (HAP) β chains were resolved into polypeptide spots with increased microheterogeneity, although these were not apparent in their sera. Their 2DE protein profiles also showed presence of hemopexin and α-1B glycoprotein, which were not detected in the profiles of the control saliva. When subjected to densitometry analysis, significant altered levels of AAT, complement C3, transferrin, transthyretin, and β chains of fibrinogen and HAP were detected. The increased levels of saliva AAT, HAP, complement C3, hemopexin, and transthyretin in the OSCC patients were validated by ELISA. The strong association of AAT and HAP with OSCC was further supported by immunohistochemical staining of cancer tissues. The differently expressed saliva proteins may be useful complementary biomarkers for the early detection and/or monitoring of OSCC, although this requires validation in clinically representative populations.
    Matched MeSH terms: Salivary Proteins and Peptides/metabolism*
  6. Absence of beta-amyloid deposition in the central nervous system of a transgenic mouse model of distal myopathy with rimmed vacuoles
    Anada RP, Wong KT, Malicdan MC, Goh KJ, Hayashi Y, Nishino I, et al.
    Amyloid, 2014 Jun;21(2):138-9.
    PMID: 24601867 DOI: 10.3109/13506129.2014.889675
    Matched MeSH terms: Amyloid beta-Peptides/metabolism*
  7. Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats
    Li Y, Tian Q, Li Z, Dang M, Lin Y, Hou X
    Drug Dev Res, 2019 09;80(6):837-845.
    PMID: 31301179 DOI: 10.1002/ddr.21567
    The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aβ1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  8. Fulltext Albumin domain mutants with enhanced Aβ binding capacity identified by phage display analysis for application in various peripheral Aβ elimination approaches of Alzheimer's disease treatment
    Ishima Y, Mimono A, Tuan Giam Chuang V, Fukuda T, Kusumoto K, Okuhira K, et al.
    IUBMB Life, 2020 04;72(4):641-651.
    PMID: 31794135 DOI: 10.1002/iub.2203
    Deposition of amyloid protein, particularly Aβ1-42 , is a major contributor to the onset of Alzheimer's disease (AD). However, almost no deposition of Aβ in the peripheral tissues could be found. Human serum albumin (HSA), the most abundant protein in the blood, has been reported to inhibit amyloid formation through binding Aβ, which is believed to play an important role in the peripheral clearance of Aβ. We identified the Aβ binding site on HSA and developed HSA mutants with high binding capacities for Aβ using a phage display method. HSA fragment 187-385 (Domain II) was found to exhibit the highest binding capacity for Aβ compared with the other two HSA fragments. To elucidate the sequence that forms the binding site for Aβ on Domain II, a random screening of Domain II display phage biopanning was constructed. A number of mutants with higher Aβ binding capacities than the wild type were identified. These mutants exhibited stronger scavenging abilities than the wild type, as revealed via in vitro equilibrium dialysis of Aβ experiments. These findings provide useful basic data for developing a safer alternative therapy than Aβ vaccines and for application in plasma exchange as well as extracorporeal dialysis.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism*
  9. Alleviatory effects of Danshen, Salvianolic acid A and Salvianolic acid B on PC12 neuronal cells and Drosophila melanogaster model of Alzheimer's disease
    Tan FHP, Ting ACJ, Leow BG, Najimudin N, Watanabe N, Azzam G
    J Ethnopharmacol, 2021 Oct 28;279:114389.
    PMID: 34217797 DOI: 10.1016/j.jep.2021.114389
    ETHNOPHARMACOLOGICAL RELEVANCE: Danshen water extract (DWE), obtained from the Salvia miltiorrhiza Bunge (Family Lamiaceae) root, is usually employed in Chinese traditional medicine as treatment to cardiovascular ailments and cerebrovascular diseases. Intriguingly, the extract was also found to contain vast beneficial properties in Alzheimer's disease (AD) treatment.

    AIM OF THE STUDY: Alzheimer's disease is the most significant type of neurodegenerative disorder plaguing societies globally. Its pathogenesis encompasses the hallmark aggregation of amyloid-beta (Aβ). Of all the Aβ oligomers formed in the brain, Aβ42 is the most toxic and aggressive. Despite this, the mechanism behind this disease remains elusive. In this study, DWE, and its major components, Salvianolic acid A (SalA) and Salvianolic acid B (SalB) were tested for their abilities to attenuate Aβ42's toxic effects.

    METHODS: The composition of DWE was determined via Ultra-Performance Liquid Chromatography (UPLC). DWE, SalA and SalB were first verified for their capability to diminish Aβ42 fibrillation using an in vitro activity assay. Since Aβ42 aggregation results in neuronal degeneration, the potential Aβ42 inhibitors were next evaluated on Aβ42-exposed PC12 neuronal cells. The Drosophila melanogaster AD model was then employed to determine the effects of DWE, SalA and SalB.

    RESULTS: DWE, SalA and SalB were shown to be able to reduce fibrillation of Aβ42. When tested on PC12 neuronal cells, DWE, SalA and SalB ameliorated cells from cell death associated with Aβ42 exposure. Next, DWE and its components were tested on the Drosophila melanogaster AD model and their rescue effects were further characterized. The UPLC analysis showed that SalA and SalB were present in the brains and bodies of Drosophila after DWE feeding. When human Aβ42 was expressed, the AD Drosophila exhibited degenerated eye structures known as the rough eye phenotype (REP), reduced lifespan and deteriorated locomotor ability. Administration of DWE, SalA and SalB partially reverted the REP, increased the age of AD Drosophila and improved most of the mobility of AD Drosophila.

    CONCLUSION: Collectively, DWE and its components may have therapeutic potential for AD patients and possibly other forms of brain diseases.

    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  10. Fulltext Alzheimer's Disease Determination by a Dual Probe on Gold Nanourchins and Nanohorn Hybrids
    Qiu Z, Shen Q, Jiang C, Yao L, Sun X, Li J, et al.
    Int J Nanomedicine, 2021;16:2311-2322.
    PMID: 33776435 DOI: 10.2147/IJN.S302396
    Background: Alzheimer's disease (AD) is a neurodegenerative chronic disorder that causes dementia and problems in thinking, cognitive impairment and behavioral changes. Amyloid-beta (Aβ) is a peptide involved in AD progression, and a high level of Aβ is highly correlated with severe AD. Identifying and quantifying Aβ levels helps in the early treatment of AD and reduces the factors associated with AD.

    Materials and Methods: This research introduced a dual probe detection system involving aptamers and antibodies to identify Aβ. Aptamers and antibodies were attached to the gold (Au) urchin and hybrid on the carbon nanohorn-modified surface. The nanohorn was immobilized on the sensor surface by using an amine linker, and then a Au urchin dual probe was immobilized.

    Results: This dual probe-modified surface enhanced the current flow during Aβ detection compared with the surface with antibody as the probe. This dual probe interacted with higher numbers of Aβ peptides and reached the detection limit at 10 fM with R2=0.992. Furthermore, control experiments with nonimmune antibodies, complementary aptamer sequences and control proteins did not display the current responses, indicating the specific detection of Aβ.

    Conclusion: Aβ-spiked artificial cerebrospinal fluid showed a similar response to current changes, confirming the selective identification of Aβ.

    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  11. Amyloid precursor protein in Alzheimer's disease
    Maurya R, Bhattacharjee G, Khambhati K, Gohil N, Singh P, Mani I, et al.
    Prog Mol Biol Transl Sci, 2023;196:261-270.
    PMID: 36813361 DOI: 10.1016/bs.pmbts.2022.09.006
    Amyloid precursor protein (APP) is a membrane protein expressed in several tissues. The occurrence of APP is predominant in synapses of nerve cells. It acts as a cell surface receptor and plays a vital role as a regulator of synapse formation, iron export and neural plasticity. It is encoded by the APP gene that is regulated by substrate presentation. APP is a precursor protein activated by proteolytic cleavage and thereby generating amyloid beta (Aβ) peptides which eventually form amyloid plaques that accumulate in Alzheimer's disease patients' brains. In this chapter, we highlight basic mechanism, structure, expression patterns and cleavage of amyloid plaques, and its diagnosis and potential treatment for Alzheimer's disease.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  12. An evidence-based review of neuronal cholesterol role in dementia and statins as a pharmacotherapy in reducing risk of dementia
    Dutta S, Rahman S, Ahmad R, Kumar T, Dutta G, Banerjee S, et al.
    Expert Rev Neurother, 2021 12;21(12):1455-1472.
    PMID: 34756134 DOI: 10.1080/14737175.2021.2003705
    INTRODUCTION: Dementia is a progressive neurodegenerative disorder impairing memory and cognition. Alzheimer's Disease, followed by vascular dementia - the most typical form. Risk factors for vascular dementia include diabetes, cardiovascular disease, hyperlipidemia. Lipids' levels are significantly associated with vascular changes in the brain.

    AREAS COVERED: The present article reviews the cholesterol metabolism in the brain, which includes: the synthesis, transport, storage, and elimination process. Additionally, it reviews the role of cholesterol in the pathogenesis of dementia and statin as a therapeutic intervention in dementia. In addition to the above, it further reviews evidence in support of as well as against statin therapy in dementia, recent updates of statin pharmacology, and demerits of use of statin pharmacotherapy.

    EXPERT OPINION: Amyloid-β peptides and intraneuronal neurofibrillary tangles are markers of Alzheimer's disease. Evidence shows cholesterol modulates the functioning of enzymes associated with Amyloid-β peptide processing and synthesis. Lowering cholesterol using statin may help prevent or delay the progression of dementia. This paper reviews the role of statin in dementia and recommends extensive future studies, including genetic research, to obtain a precise medication approach for patients with dementia.

    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  13. An in silico approach towards the identification of novel inhibitors of the TLR-4 signaling pathway
    Mahita J, Harini K, Rao Pichika M, Sowdhamini R
    J Biomol Struct Dyn, 2016 Jun;34(6):1345-62.
    PMID: 26264972 DOI: 10.1080/07391102.2015.1079243
    Precise functioning and fine-tuning of Toll-like receptor 4 (TLR4) signaling is a critical requirement for the smooth functioning of the innate immune system, since aberrant TLR4 activation causes excessive production of pro-inflammatory cytokines and interferons. This can result in life threatening conditions such as septic shock and other inflammatory disorders. The TRIF-related adaptor molecule (TRAM) adaptor protein is unique to the TLR4 signaling pathway and abrogation of TRAM-mediated TLR4 signaling is a promising strategy for developing therapeutics aimed at disrupting TRAM interactions with other components of the TLR4 signaling complex. The VIPER motif from the vaccinia virus-producing protein, A46 has been reported to disrupt TRAM-TLR4 interactions. We have exploited this information, in combination with homology modeling and docking approaches, to identify a potential binding site on TRAM lined by the BB loop and αC helix. Virtual screening of commercially available small molecules targeting the binding site enabled to short-list 12 small molecules to abrogate TRAM-mediated TLR4 signaling. Molecular dynamics and molecular mechanics calculations have been performed for the analysis of these receptor-ligand interactions.
    Matched MeSH terms: Peptides/metabolism
  14. Angiotensin I-converting enzyme inhibitory activity and bioconversion of isoflavones by probiotics in soymilk supplemented with prebiotics
    Yeo SK, Liong MT
    Int J Food Sci Nutr, 2010 Mar;61(2):161-81.
    PMID: 20085504 DOI: 10.3109/09637480903348122
    Lactobacillus sp. FTDC 2113, L. acidophilus FTDC 8033, L. acidophilus ATCC 4356, L. casei ATCC 393, Bifidobacterium FTDC 8943 and B. longum FTDC 8643 were incorporated into soymilk supplemented with fructooligosaccharides (FOS), inulin, mannitol, maltodextrin and pectin. The objective of the present study was to evaluate the effects of prebiotics on the bioactivity of probiotic-fermented soymilk. Proteolytic activity was increased in the presence of FOS, while the supplementation of inulin and pectin increased the angiotensin I-converting enzyme inhibitory activity accompanied by lower IC(50) values. The beta-glucosidase activity was also enhanced in the presence of pectin. This led to higher bioconversion of glucosides to aglycones by probiotics, especially genistin and malonyl genistin to genistein. Results from this study indicated that the supplementation of prebiotics enhanced the in-vitro antihypertensive effect and production of bioactive aglycones in probiotic-fermented soymilk. Therefore, this soymilk could potentially be used as a dietary therapy to reduce the risks of hypertension and hormone-dependent diseases such as breast cancer, prostate cancer and osteoporosis.
    Matched MeSH terms: Peptides/metabolism
  15. Anti-nociceptive mechanisms of flavonoids-rich methanolic extract from Terminalia coriacea (Roxb.) Wight & Arn. leaves
    Ali Khan MS, Ahmed N, Misbah, Arifuddin M, Zakaria ZA, Al-Sanea MM, et al.
    Food Chem Toxicol, 2018 May;115:523-531.
    PMID: 29555329 DOI: 10.1016/j.fct.2018.03.021
    In view of the report on anti-nociceptive activity of Leathery Murdah, Terminalia coriacea {Roxb.} Wight & Arn. (Combretaceae) leaves, the present study was conducted to isolate the active constituents and identify the underlying mechanisms. The methanolic extract of T. coriacea leaves (TCLME) at doses 125, 250 and 500 mg/kg orally, was subjected to various in-vivo assays in acetic acid induced writhing and formalin induced paw-licking tests with aspirin (100 mg/kg) and morphine (5 mg/kg) as reference drugs. Three flavonoids, rutin, robinin and gossypetin 3-glucuronide 8-glucoside were isolated and characterized from TCLME for the first time. The extract showed significant (p 
    Matched MeSH terms: Opioid Peptides/metabolism
  16. Antioxidative peptides from food proteins: a review
    Sarmadi BH, Ismail A
    Peptides, 2010 Oct;31(10):1949-56.
    PMID: 20600423 DOI: 10.1016/j.peptides.2010.06.020
    Bioactive peptides, as products of hydrolysis of diverse food proteins, are the focus of current research. They exert various biological roles, one of the most crucial of which is the antioxidant activity. Reverse relationship between antioxidant intake and diseases has been approved through plenty of studies. Antioxidant activity of bioactive peptides can be attributed to their radical scavenging, inhibition of lipid peroxidation and metal ion chelation properties of peptides. It also has been proposed that peptide structure and its amino acid sequence can affect its antioxidative properties. This paper reviews bioactive peptides from food sources concerning their antioxidant activities. Additionally, specific characteristics of antioxidative bioactive peptides, enzymatic production, methods to evaluate antioxidant capacity, bioavailability, and safety concerns of peptides are reviewed.
    Matched MeSH terms: Peptides/metabolism*
  17. Fulltext Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide
    Rothan HA, Mohamed Z, Suhaeb AM, Rahman NA, Yusof R
    OMICS, 2013 Nov;17(11):560-7.
    PMID: 24044366 DOI: 10.1089/omi.2013.0056
    Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.
    Matched MeSH terms: Peptides/metabolism
  18. Behavioural Effects and RNA-seq Analysis of Aβ42-Mediated Toxicity in a Drosophila Alzheimer's Disease Model
    Tan FHP, Azzam G, Najimudin N, Shamsuddin S, Zainuddin A
    Mol Neurobiol, 2023 Aug;60(8):4716-4730.
    PMID: 37145377 DOI: 10.1007/s12035-023-03368-x
    Alzheimer's disease (AD) is the most common neurological ailment worldwide. Its process comprises the unique aggregation of extracellular senile plaques composed of amyloid-beta (Aβ) in the brain. Aβ42 is the most neurotoxic and aggressive of the Aβ42 isomers released in the brain. Despite much research on AD, the complete pathophysiology of this disease remains unknown. Technical and ethical constraints place limits on experiments utilizing human subjects. Thus, animal models were used to replicate human diseases. The Drosophila melanogaster is an excellent model for studying both physiological and behavioural aspects of human neurodegenerative illnesses. Here, the negative effects of Aβ42-expression on a Drosophila AD model were investigated through three behavioural assays followed by RNA-seq. The RNA-seq data was verified using qPCR. AD Drosophila expressing human Aβ42 exhibited degenerated eye structures, shortened lifespan, and declined mobility function compared to the wild-type Control. RNA-seq revealed 1496 genes that were differentially expressed from the Aβ42-expressing samples against the control. Among the pathways that were identified from the differentially expressed genes include carbon metabolism, oxidative phosphorylation, antimicrobial peptides, and longevity-regulating pathways. While AD is a complicated neurological condition whose aetiology is influenced by a number of factors, it is hoped that the current data will be sufficient to give a general picture of how Aβ42 influences the disease pathology. The discovery of molecular connections from the current Drosophila AD model offers fresh perspectives on the usage of this Drosophila which could aid in the discovery of new anti-AD medications.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  19. Beyond the Obvious: Smoking and Respiratory Infection Implications on Alzheimer's Disease
    Wadhwa R, Paudel KR, Mehta M, Shukla SD, Sunkara K, Prasher P, et al.
    CNS Neurol Disord Drug Targets, 2020;19(9):698-708.
    PMID: 33109069 DOI: 10.2174/1871527319999200817112427
    Tobacco smoke is not only a leading cause for chronic obstructive pulmonary disease, cardiovascular disorders, and lung and oral cancers, but also causes neurological disorders such as Alzheimer 's disease. Tobacco smoke consists of more than 4500 toxic chemicals, which form free radicals and can cross blood-brain barrier resulting in oxidative stress, an extracellular amyloid plaque from the aggregation of amyloid β (Aβ) peptide deposition in the brain. Further, respiratory infections such as Chlamydia pneumoniae, respiratory syncytial virus have also been involved in the induction and development of the disease. The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. The review article sheds light on the role of smoking and respiratory infections in causing oxidative stress and neuroinflammation, resulting in Alzheimer's disease (AD). This review will be of interest to scientists and researchers from biological and medical science disciplines, including microbiology, pharmaceutical sciences and the translational researchers, etc. The increasing understanding of the relationship between chronic lung disease and neurological disease is two-fold. First, this would help to identify the risk factors and possible therapeutic interventions to reduce the development and progression of both diseases. Second, this would help to reduce the probable risk of development of AD in the population prone to chronic lung diseases.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  20. Binding specificity of polypeptide substrates in NS2B/NS3pro serine protease of dengue virus type 2: A molecular dynamics Study
    Yotmanee P, Rungrotmongkol T, Wichapong K, Choi SB, Wahab HA, Kungwan N, et al.
    J Mol Graph Model, 2015 Jul;60:24-33.
    PMID: 26086900 DOI: 10.1016/j.jmgm.2015.05.008
    The pathogenic dengue virus (DV) is a growing global threat, particularly in South East Asia, for which there is no specific treatment available. The virus possesses a two-component (NS2B/NS3) serine protease that cleaves the viral precursor proteins. Here, we performed molecular dynamics simulations of the NS2B/NS3 protease complexes with six peptide substrates (capsid, intNS3, 2A/2B, 4B/5, 3/4A and 2B/3 containing the proteolytic site between P(1) and P(1)' subsites) of DV type 2 to compare the specificity of the protein-substrate binding recognition. Although all substrates were in the active conformation for cleavage reaction by NS2B/NS3 protease, their binding strength was somewhat different. The simulated results of intermolecular hydrogen bonds and decomposition energies suggested that among the ten substrate residues (P(5)-P(5)') the P(1) and P(2) subsites play a major role in the binding with the focused protease. The arginine residue at these two subsites was found to be specific preferential binding at the active site with a stabilization energy of intNS3>2A/2B>4B/5>3/4A>2B/3 in a relative correspondence with previous experimentally derived values.
    Matched MeSH terms: Peptides/metabolism
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