Rahman MA

References (10)

Title : Multicomponent Petasis reaction for the identification of pyrazine based multi-target directed anti-Alzheimer's agents: In-silico design, synthesis, and characterization - Madhav_2023_Eur.J.Med.Chem_254_115354
Author(s) : Madhav H , Abdel-Rahman SA , Hashmi MA , Rahman MA , Rehan M , Pal K , Nayeem SM , Gabr MT , Hoda N
Ref : Eur Journal of Medicinal Chemistry , 254 :115354 , 2023
Abstract : Multi-target directed ligands (MTDLs) have recently attracted significant interest due to their exceptional effectiveness against multi-factorial Alzheimer's disease. The present work described the development of pyrazine-based MTDLs using multicomponent Petasis reaction for the dual inhibition of tau-aggregation and human acetylcholinesterase (hAChE). The molecular structure of synthesized ligands was validated by (1)H & (13)C NMR and mass spectrometry. The screened compounds were shown to have a strong inhibitory effect at 10 microM concentration against tau-oligomerization and hAChE, but only moderate inhibitory activity against Abeta(42). Among all the compounds, the half-maximal inhibitory concentration (IC(50)) for 21 and 24 against hAChE were 0.71 microM and 1.09 microM, respectively, while they displayed half-maximal effective concentrations (EC(50)) values of 2.21 microM and 2.71 microM for cellular tau-oligomerization, respectively. Additionally, an MTT experiment using tau-expressing SH-SY5Y neuroblastoma cells revealed that 21 was more neuroprotective than the FDA-approved medication donepezil. Furthermore, an MD simulation study was performed to investigate the dynamics and stability of AChE-21 and AChE-24 complexes in an aqueous environment. The MM-PBSA calculations were performed to evaluate the binding of 21 and 24 with AChE, and the relative binding energy was calculated as -870.578 and -875.697 kJ mol(-1), respectively. As a result, the study offered insight into the design of new MTDLs and highlighted 21 as a potential roadblock to the development of anti-AD medications.
ESTHER : Madhav_2023_Eur.J.Med.Chem_254_115354
PubMedSearch : Madhav_2023_Eur.J.Med.Chem_254_115354
PubMedID: 37043996

Title : Protective role of hydroalcoholic extract of Cajanus cajan Linn leaves against memory impairment in sleep deprived experimental rats - Ahmad_2020_J.Ayurveda.Integr.Med_11_471
Author(s) : Ahmad L , Mujahid M , Mishra A , Rahman MA
Ref : J Ayurveda Integr Med , 11 :471 , 2020
Abstract : BACKGROUND: The plant Cajanus cajan had earlier shown protective effect against hypoxic-ischemic brain damage in rats. OBJECTIVE: Hence, hydroalcoholic extract of C. cajan Linn leaves (HECC) was evaluated for its protective role against memory impairment in sleep-deprived Sprague Dawley rats. MATERIALS AND METHODS: Adult rats were divided into five groups each consisting of 5 rats (n = 5). Groups I, II, III, IV and V received 1 mL/kg 1% CMC, 1 mL/kg 1% CMC, 200 mg/kg HECC, 400 mg/kg HECC and 200 mg/kg piracetam respectively as per b.wt. orally everyday for 14 days. Animals of every groups except group-I were subjected to sleep-deprivation from 15th to 19th day for induction of memory impairment. Behavioral activities i.e., elevated plus maze test and locomotor activity were evaluated. Afterwards, brain was isolated from the sacrificed animals for biochemical investigation of acetylcholinesterase (AChE); antioxidant activities i.e., catalase (CAT), superoxide dismutase (SOD), lipid peroxide; and histopathological changes. RESULTS: The percent number of entries, number of entries in open arm, AChE activity, lipid peroxide activity of HECC-treated group-III and group-IV were significantly (p < 0.01) decreased while, their CAT and SOD activities were significantly (p < 0.01) increased in dose-dependent manner as compared to sleep-deprived group-II. The activities of group-IV were almost significantly equivalent to that of piracetam-treated group-V. Protective effect of HECC was well supported with brain's histopathology. CONCLUSION: HECC possesses a protective effect against memory impairment indicating its therapeutic efficacy against memory loss as in Alzheimer's disease. Probable underlying mechanisms may be brain's AChE inhibition and increased antioxidant potential by HECC.
ESTHER : Ahmad_2020_J.Ayurveda.Integr.Med_11_471
PubMedSearch : Ahmad_2020_J.Ayurveda.Integr.Med_11_471
PubMedID: 30661946

Title : Cholinesterase research outreach project (CROP): point of care cholinesterase measurement in an Australian agricultural community - Cotton_2018_Environ.Health_17_31
Author(s) : Cotton J , Edwards J , Rahman MA , Brumby S
Ref : Environ Health , 17 :31 , 2018
Abstract : BACKGROUND: Australian farmers are routinely exposed to a wide variety of agrichemicals, including herbicides and insecticides. Organophosphate (OP) insecticides are widely used for agricultural production, horticulture and animal husbandry practices. Symptoms of OP toxicity are the results of inhibition of the enzyme acetylcholinesterase (AChE) which is found in many types of conducting tissue in human bodies such as nerve and muscle, central and peripheral tissues, motor and sensory fibres. Cholinesterase can be measured in red blood cells/erythrocytes (AChE) and plasma (PChE). This study aims to explore integration of AChE monitoring into routine health checks for those at risk and also to examine any association between AChE activity and agrichemical use in a Victorian farming community in Australia. METHODS: This was a prospective cohort study, where farmers and non-famers were compared on the levels of AChE at four time points of baseline, 3-4 weeks, 6-weeks and at 9-weeks. Study participants (N = 55) were residents from South West Victoria, aged between 18 and 75 years, spoke English, and had not had a previous known acute chemical accident. A total of 41 farming (had been farming for more than 5 years) and a convenience sample of 14 non-farming individuals met the inclusion criteria. Testing of AChE was repeated for all participants with a maximum of three times over 10 weeks. RESULTS: The integration of AChE monitoring was very well accepted by all participants. There was no significant difference in average AChE activity between farming and non-farming participants (one-way ANOVA p > 0.05) in this study. There was no significant difference between personal use of agricultural chemicals on farm and the levels of AChE at baseline (measurement 1) or any of the follow up periods (p > 0.05). However, the mean activity of AChE was significantly lower within follow up periods [F (2.633, 139.539) = 14.967, p < 0.001]. There was a significant reduction of AChE between the follow up at 3-weeks and 6-weeks period (p = 0.015). CONCLUSIONS: The routine monitoring of AChE may allow for early recognition of chronic low-level exposure to OPs when they are used by farmers, provided a reasonable estimate of baseline AChE is available. This work provides an evidence for recommending the integration of AChE monitoring into point of care (POC) procedures in rural health clinics and quantifying pesticide exposure and personal protection both on the farm and in the home. Farmer engagement is crucial to the successful integration of AChE monitoring into rural health clinics in Australia. TRIAL REGISTRATION: ACTRN12613001256763 .
ESTHER : Cotton_2018_Environ.Health_17_31
PubMedSearch : Cotton_2018_Environ.Health_17_31
PubMedID: 29606131

Title : Splicing regulation and dysregulation of cholinergic genes expressed at the neuromuscular junction - Ohno_2017_J.Neurochem_142 Suppl 2_64
Author(s) : Ohno K , Rahman MA , Nazim M , Nasrin F , Lin Y , Takeda JI , Masuda A
Ref : Journal of Neurochemistry , 142 Suppl 2 :64 , 2017
Abstract : We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction are also alternatively spliced. In addition, germline mutations provoke aberrant splicing by compromising binding of RNA-binding proteins, and cause congenital myasthenic syndromes (CMS). We present physiological splicing mechanisms of genes for agrin (AGRN), acetylcholinesterase (ACHE), MuSK (MUSK), acetylcholine receptor (AChR) alpha1 subunit (CHRNA1), and collagen Q (COLQ) in human, and their aberration in diseases. Splicing isoforms of AChET , AChEH , and AChER are generated by hnRNP H/F. Skipping of MUSK exon 10 makes a Wnt-insensitive MuSK isoform, which is unique to human. Skipping of exon 10 is achieved by coordinated binding of hnRNP C, YB-1, and hnRNP L to exon 10. Exon P3A of CHRNA1 is alternatively included to generate a non-functional AChR alpha1 subunit in human. Molecular dissection of splicing mutations in patients with CMS reveals that exon P3A is alternatively skipped by hnRNP H, polypyrimidine tract-binding protein 1, and hnRNP L. Similarly, analysis of an exonic mutation in COLQ exon 16 in a CMS patient discloses that constitutive splicing of exon 16 requires binding of serine arginine-rich splicing factor 1. Intronic and exonic splicing mutations in CMS enable us to dissect molecular mechanisms underlying alternative and constitutive splicing of genes expressed at the neuromuscular junction. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.
ESTHER : Ohno_2017_J.Neurochem_142 Suppl 2_64
PubMedSearch : Ohno_2017_J.Neurochem_142 Suppl 2_64
PubMedID: 28072465

Title : Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms -
Author(s) : Nazim M , Masuda A , Rahman MA , Nasrin F , Takeda JI , Ohe K , Ohkawara B , Ito M , Ohno K
Ref : Nucleic Acids Research , 45 :1455 , 2017
PubMedID: 28180311

Title : Immobilization of a novel cold active esterase onto FeO approximately cellulose nano-composite enhances catalytic properties - Rahman_2016_Int.J.Biol.Macromol_87_488
Author(s) : Rahman MA , Culsum U , Kumar A , Gao H , Hu N
Ref : Int J Biol Macromol , 87 :488 , 2016
Abstract : A novel esterase, EstH was cloned, purified and characterized from the marine bacterium Zunongwangia sp. The purified EstH showed optimum activity at 30 degrees C and pH 8.5 with approximately 50% of original activity at 0 degrees C. EstH was stable in high salt conditions (0-4.5M NaCl). To improve the characteristics and explore the possibilities for application, a new immobilization matrix, Fe3O4 approximately cellulose nano-composite, was prepared and was characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM). Interestingly the optimal temperature of immobilized EstH elevated to 35 degrees C. Compared to its free form, immobilized EstH showed better temperature stability (48.5% compared to 22.40% at 50 degrees C after 30min), prolonged half-life (32h compared to 18h), higher storage stability ( approximately 71% activity compared to approximately 40% after 50days of storage), improved pH tolerance ( approximately 73% activity at pH 4 and 10), and, more importantly, reusability ( approximately 50% activity after 8 repetitive cycles of usage). Enzyme kinetics showed an increase in the Vmax (from 35.76 to 51.14muM/min) and Kcat (from 365s-1 to 520s-1) after immobilization. The superior catalytic properties of immobilized EstH suggest its great potential in biotechnology and industrial processes.
ESTHER : Rahman_2016_Int.J.Biol.Macromol_87_488
PubMedSearch : Rahman_2016_Int.J.Biol.Macromol_87_488
PubMedID: 26976070

Title : Characterization of a novel cold active and salt tolerant esterase from Zunongwangia profunda - Rahman_2016_Enzyme.Microb.Technol_85_1
Author(s) : Rahman MA , Culsum U , Tang W , Zhang SW , Wu G , Liu Z
Ref : Enzyme Microb Technol , 85 :1 , 2016
Abstract : A novel cold active esterase, EstLiu was cloned from the marine bacterium Zunongwangia profunda, overexpressed in E. coli BL21 (DE3) and purified by glutathione-S transferase (GST) affinity chromatography. The mature esterase EstLiu sequence encodes a protein of 273 amino acids residues, with a predicted molecular weight of 30KDa and containing the classical pentapeptidase motif from position 156 to 160 with the catalytic triad Ser158-Asp211-His243. Although, EstLiu showed 64% similarity with the hypothetical esterase from Chryseobacterium sp. StRB126 (WP_045498424), phylogenetic analysis showed it had no similarity with any of the established family of lipases/esterases, suggesting that it could be considered as a new family. The purified enzyme showed broad substrate specificity with the highest hydrolytic activity against p-nitrophenyl butyrate (C4). EstLiu showed remarkable activity (75%) at 0 degrees Cand the optimal activity at pH 8.0 and 30 degrees C with good thermostability and quickened inactivation above 60 degrees C. EstLiu retained 81, 103, 67 and 78% of its original activity at 50% (v/v) in ethanol, isopropanol, DMSO and ethylene glycol, respectively. In the presence of Tween 20, Tween 80 and Triton X-100, EstLiu showed 88, 100 and 117% of relative activity. It is also co-factor independent. The high activity at low temperature and desirable stability in organic solvents and salts of this novel family esterase represents a good evidence of novel biocatalyst. Overall, this novel enzyme showed better activity than previously reported esterases in extreme reaction conditions and could promote the reaction in both aqueous and non-aqueous conditions, indicating its great potential for industrial applications.
ESTHER : Rahman_2016_Enzyme.Microb.Technol_85_1
PubMedSearch : Rahman_2016_Enzyme.Microb.Technol_85_1
PubMedID: 26920474

Title : SRSF1 and hnRNP H antagonistically regulate splicing of COLQ exon 16 in a congenital myasthenic syndrome - Rahman_2015_Sci.Rep_5_13208
Author(s) : Rahman MA , Azuma Y , Nasrin F , Takeda J , Nazim M , Ahsan KB , Masuda A , Engel AG , Ohno K
Ref : Sci Rep , 5 :13208 , 2015
Abstract : The catalytic subunits of acetylcholinesterase (AChE) are anchored in the basal lamina of the neuromuscular junction using a collagen-like tail subunit (ColQ) encoded by COLQ. Mutations in COLQ cause endplate AChE deficiency. An A-to-G mutation predicting p.E415G in COLQ exon 16 identified in a patient with endplate AChE deficiency causes exclusive skipping of exon 16. RNA affinity purification, mass spectrometry, and siRNA-mediated gene knocking down disclosed that the mutation disrupts binding of a splicing-enhancing RNA-binding protein, SRSF1, and de novo gains binding of a splicing-suppressing RNA-binding protein, hnRNP H. MS2-mediated artificial tethering of each factor demonstrated that SRSF1 and hnRNP H antagonistically modulate splicing by binding exclusively to the target in exon 16. Further analyses with artificial mutants revealed that SRSF1 is able to bind to degenerative binding motifs, whereas hnRNP H strictly requires an uninterrupted stretch of poly(G). The mutation compromised splicing of the downstream intron. Isolation of early spliceosome complex revealed that the mutation impairs binding of U1-70K (snRNP70) to the downstream 5' splice site. Global splicing analysis with RNA-seq revealed that exons carrying the hnRNP H-binding GGGGG motif are predisposed to be skipped compared to those carrying the SRSF1-binding GGAGG motif in both human and mouse brains.
ESTHER : Rahman_2015_Sci.Rep_5_13208
PubMedSearch : Rahman_2015_Sci.Rep_5_13208
PubMedID: 26282582

Title : Neurexin Ibeta and neuroligin are localized on opposite membranes in mature central synapses - Berninghausen_2007_J.Neurochem_103_1855
Author(s) : Berninghausen O , Rahman MA , Silva JP , Davletov B , Hopkins C , Ushkaryov YA
Ref : Journal of Neurochemistry , 103 :1855 , 2007
Abstract : Synaptogenesis requires formation of trans-synaptic complexes between neuronal cell-adhesion receptors. Heterophilic receptor pairs, such as neurexin Ibeta and neuroligin, can mediate distinct intracellular signals and form different cytoplasmic scaffolds in the pre- and post-synaptic neuron, and may be particularly important for synaptogenesis. However, the functions of neurexin and neuroligin depend on their distribution in the synapse. Neuroligin has been experimentally assigned to the post-synaptic membrane, while the localization of neurexin remains unclear. To study the subcellular distribution of neurexin Ibeta and neuroligin in mature cerebrocortical synapses, we have developed a novel method for the physical separation of junctional membranes and their direct analysis by western blotting. Using urea and dithiothreitol, we disrupted trans-synaptic protein links, without dissolving the lipid phase, and fractionated the pre- and post-synaptic membranes. The purity of these fractions was validated by electron microscopy and western blotting using multiple synaptic markers. A quantitative analysis has confirmed that neuroligin is localized strictly in the post-synaptic membrane. We have also demonstrated that neurexin Ibeta is largely (96%) pre-synaptic. Thus, neurexin Ibeta and neuroligin normally form trans-synaptic complexes and can transduce bidirectional signals.
ESTHER : Berninghausen_2007_J.Neurochem_103_1855
PubMedSearch : Berninghausen_2007_J.Neurochem_103_1855
PubMedID: 17868325
Gene_locus related to this paper: human-NLGN3 , human-NLGN4X

Title : Genome sequence of the cat pathogen, Chlamydophila felis - Azuma_2006_DNA.Res_13_15
Author(s) : Azuma Y , Hirakawa H , Yamashita A , Cai Y , Rahman MA , Suzuki H , Mitaku S , Toh H , Goto S , Murakami T , Sugi K , Hayashi H , Fukushi H , Hattori M , Kuhara S , Shirai M
Ref : DNA Research , 13 :15 , 2006
Abstract : Chlamydophila felis (Chlamydia psittaci feline pneumonitis agent) is a worldwide spread pathogen for pneumonia and conjunctivitis in cats. Herein, we determined the entire genomic DNA sequence of the Japanese C. felis strain Fe/C-56 to understand the mechanism of diseases caused by this pathogen. The C. felis genome is composed of a circular 1,166,239 bp chromosome encoding 1005 protein-coding genes and a 7552 bp circular plasmid. Comparison of C. felis gene contents with other Chlamydia species shows that 795 genes are common in the family Chlamydiaceae species and 47 genes are specific to C. felis. Phylogenetic analysis of the common genes reveals that most of the orthologue sets exhibit a similar divergent pattern but 14 C. felis genes accumulate more mutations, implicating that these genes may be involved in the evolutional adaptation to the C. felis-specific niche. Gene distribution and orthologue analyses reveal that two distinctive regions, i.e. the plasticity zone and frequently gene-translocated regions (FGRs), may play important but different roles for chlamydial genome evolution. The genomic DNA sequence of C. felis provides information for comprehension of diseases and elucidation of the chlamydial evolution.
ESTHER : Azuma_2006_DNA.Res_13_15
PubMedSearch : Azuma_2006_DNA.Res_13_15
PubMedID: 16766509
Gene_locus related to this paper: chlff-q253e0 , chlff-q254l8