Ali G

References (12)

Title : Neuroprotective evaluation of diospyrin against drug-induced Alzheimer's disease - Alam_2023_Fitoterapia_171_105703
Author(s) : Alam A , Ali G , Nawaz A , AlOmar TS , Rauf A , Ayaz M , Ahmad S , Almasoud N , AlOmar AS , Khalil AA , Wilairatana P
Ref : Fitoterapia , 171 :105703 , 2023
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disease linked to memory impairment. A current investigation was performed to assess the neuroprotective effect of Diospyrin, a novel therapeutic agent, for the curing of Alzheimer's disease. For this purpose, in-vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory assays and antioxidant studies were conducted, whereas in-vivo studies involved different behavioral animal models tests such as elevated plus maze (EPM), morris water maze (MWM) and paddling Y-maze test. Results of the in-vitro analysis showed IC(50) values of 95 microg/mL for AChE and 110 microg/mL for BChE as compared to the standard drug donepezil (IC(50): 95 & 85 microg/mL, respectively). DPPH antioxidant assay showed a maximum of 72.85% inhibition (IC(50): 139.74 microg/mL) of DPPH-free radicals at the highest concentration of 1000 microg/mL as compared to the ascorbic acid (IC(50): 13.72 microg/mL). Moreover, the in-vivo analysis revealed that diospyrin treatment demonstrated gradual betterment in memory and enhanced motor functionality. On the other hand, the computational analysis also showed that the diospyrin had exceptional binding affinities for both AChE and BChE enzymes. In the net shell, it may be deduced that our compound diospyrin could be a valuable drug candidate in managing neurodegenerative disorders like AD.
ESTHER : Alam_2023_Fitoterapia_171_105703
PubMedSearch : Alam_2023_Fitoterapia_171_105703
PubMedID: 37852388

Title : Attenuation of spatial memory in 5xFAD mice by targeting cholinesterases, oxidative stress and inflammatory signaling using 2-(hydroxyl-(2-nitrophenyl)methyl)cyclopentanone - Ullah_2021_Int.Immunopharmacol_100_108083
Author(s) : Ullah R , Ali G , Subhan F , Khan A , Ahsan Halim S , Naveed M , Kalsoom S , Al-Harrasi A
Ref : Int Immunopharmacol , 100 :108083 , 2021
Abstract : Alzheimer's disease (AD) is classified pathologically as a progressive neurological disorder associated with memory decline. The study was designed to assess the underlying molecular signaling involved in the neuroprotective effect of the 2-(hydroxyl-(2-nitrophenyl)methyl)cyclopentanone (2NCP) as a novel therapeutic agent for AD. In this connection, in vitro cholinesterases inhibitory and antioxidant activities were investigated. In vivo studies were carried out on a well-known 5xFAD mice model in different behavioural models such as light/dark box,balance beam, rotarod, elevated plus maze (EPM),novel object recognition (NOR), paddling Y-maze, and Morris water maze (MWM) tests. Hippocampus (HC) and frontal cortex (FC) homogenates were examined for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals, glutathione S-transferase (GST), glutathione (GSH), and catalase. Further, we examined the expression of inflammatory cytokines and Nrf2 in the HC and FC through RT-PCR. Computational studies were conducted to predict the binding mode of the 2NCP with target sites of nuclear factor-kappaB (NF-kappaB) and cholinesterases. The findings of in vitro assays revealed that the IC(50) values of the 2NCP against AChE and BChE were 17 and 23 microg/ml respectively. DPPH antioxidant assay displayed an IC(50) value for the 2NCP was 62 microg/ml. Whereas, theex vivo study depicted that the activities of AChE and BChEwere significantly reduced. Moreover, free radicals load, GSH level, catalase and GST activities were significantly declined. Furthermore, in vivostudies showed that the 2NCP treated animals exhibited gradual memory improvement and improved motor functions. RT-PCR study revealed that mRNA levels of the inflammatory mediators (IL-1beta, IL-6, TNF-alpha) were significantly reduced, while the expression of antioxidant Nrf2 was significantly increased.The molecular docking studies further confirmed that the 2NCP showed excellent binding affinities for NF-kappaB and cholinesterases. Taken together, the 2NCP improves spatial memory and learning, short- and long-term memory,markedly inhibits cholinesterases, reduced neuroinflammation, and mitigated oxidative stress in the 5xFAD mice; hence the 2NCP may be a potential candidate for the management of AD.
ESTHER : Ullah_2021_Int.Immunopharmacol_100_108083
PubMedSearch : Ullah_2021_Int.Immunopharmacol_100_108083
PubMedID: 34478946

Title : Synthetic beta-hydroxy ketone derivative inhibits cholinesterases, rescues oxidative stress and ameliorates cognitive deficits in 5XFAD mice model of AD - Ahmad_2020_Mol.Biol.Rep_47_9553
Author(s) : Ahmad SI , Ali G , Muhammad T , Ullah R , Umar MN , Hashmi AN
Ref : Mol Biol Rep , 47 :9553 , 2020
Abstract : Alzheimer's disease (AD) is a progressive, chronic and age-related neurodegenerative disorder that affects millions of people across the world. In pursuit of new anti-AD remedies, 2-[Hydroxy-(4-nitrophenyl)methyl]-cyclopentanone (NMC), a beta hydroxyl ketone derivative was studied to explore its neuroprotective potentials against AD. The in-vitro AChE and BuChE enzymes inhibition were evaluated by Ellman protocol and antioxidant potentials of NMC by DPPH free radical scavenging assay. In-vivo behavioral studies were performed in the transgenic 5xFAD mice model of AD using shallow water maze (SWM), Paddling Y-Maze (PYM), elevated plus maze (EPM) and balance beam (BB) tests. Also, the ex-vivo cholinesterase inhibitory effects of NMC and histopathological analysis of amyloid-beta plaques were determined in the frontal cortex and hippocampal regions of the mice brain. NMC exhibited significant in vitro anti-cholinesterase enzyme potentials with an IC(50) value of 67 microg/ml against AChE and 96 microg/ml against BuChE respectively. Interestingly, the activities of AChE and BuChE enzymes were also significantly lower in the cortex and hippocampus of NMC-treated groups. Also, in the DPPH assessment, NMC displayed substantial antioxidant properties with an IC(50) value observed as 171 microg/ml. Moreover, histopathological analysis via thioflavin-s staining displayed significantly lower plaques depositions in the cortex and hippocampus region of NMC-treated mice groups. Furthermore, SWM, PYM, EPM, and BB behavioral analysis indicated that NMC enhanced spatial learning, memory consolidation and improved balance performance. Altogether, to the best of our knowledge, we believe that NMC may serve as a potential and promising anti-cholinesterase, antioxidant and neuroprotective agent against AD.
ESTHER : Ahmad_2020_Mol.Biol.Rep_47_9553
PubMedSearch : Ahmad_2020_Mol.Biol.Rep_47_9553
PubMedID: 33211296

Title : Attenuation of Spatial Memory in 5xFAD Mice by Halting Cholinesterases, Oxidative Stress and Neuroinflammation Using a Cyclopentanone Derivative - Ullah_2020_Pharmaceuticals.(Basel)_13_
Author(s) : Ullah R , Ali G , Ahmad N , Akram M , Kumari G , Amin MU , Umar MN
Ref : Pharmaceuticals (Basel) , 13 : , 2020
Abstract : Alzheimer's disease (AD) is an irreversible and chronic neurological disorder that gradually destroys memory and thinking skills. The research study was designed to investigate the underlying molecular signaling involved in the neuroprotective effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) as a therapeutic agent for AD. In this study, In vivo studies were carried out on a well-known 5xFAD mice model using different behavioural test models such as open field, rotarod, Morris water maze (MWM), and Y-maze tests. Furthermore, in vitro cholinesterase inhibition activity assays were carried out. The frontal cortex (FC) and hippocampus (HC) homogenates were tested for the levels/activities of cholinesterases, glutathione (GSH), glutathione S-transferase (GST), and catalase. Furthermore, the hippocampal expression of inflammatory cytokines was observed via RT-PCR and western blot. The results of in vivo studies show an enhancement in the learning behavior. The 3NCP treatment reduced latency time in MWM and Y-maze tests, also increase spontaneous alternation indicate significant effect of 3NCP on memory. Furthermore, open field and rotarod studies revealed that 3NCP does not cause motor coordination deficit. The results of the in vitro studies revealed that the IC(50) values of the 3NCP against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were 16.17 and 20.51 microg/mL, respectively. This decline in AChE and BChE was further supported by ex vivo studies. Further, the 3NCP mitigates the GSH level, GST, and catalase activities in HC and FC. The mRNA and protein expression of inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) markedly declined in RT-PCR and western blotting. The results of the current study conclusively demonstrate that 3NCP reduces oxidative stress and mitigates neuroinflammation in 5xFAD mice, implying that 3NCP may be a potential therapeutic candidate for AD treatment in the future.
ESTHER : Ullah_2020_Pharmaceuticals.(Basel)_13_
PubMedSearch : Ullah_2020_Pharmaceuticals.(Basel)_13_
PubMedID: 33086500

Title : Anti-Alzheimer's Studies on beta-Sitosterol Isolated from Polygonum hydropiper L - Ayaz_2017_Front.Pharmacol_8_697
Author(s) : Ayaz M , Junaid M , Ullah F , Subhan F , Sadiq A , Ali G , Ovais M , Shahid M , Ahmad A , Wadood A , El-Shazly M , Ahmad N , Ahmad S
Ref : Front Pharmacol , 8 :697 , 2017
Abstract : The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer's disease (AD). In search of new anti-AD drugs, beta-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer's agent. The in vitro AChE, BChE inhibitory potentials of beta-sitosterol were investigated following Ellman's assay. The antioxidant activity was tested using DPPH, ABTS and H2O2 assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. beta-sitosterol was tested for in vivo inhibitory potentials against cholinesterase's and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of beta-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo cholinesterase inhibitory effects were observed in the beta-sitosterol treated groups. beta-sitosterol exhibited an IC50 value of 55 and 50 mug/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of beta-sitosterol with the target enzyme and further support the in vitro and in vivo results. In the antioxidant assays, the IC50 values were observed as 140, 120, and 280 mug/ml in the DPPH, ABTS and H2O2 assays respectively. The free radicals load in the brain tissues was significantly declined in the beta-sitosterol treated animals as compared to the transgenic-saline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, beta-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that beta-sitosterol is a potential compound for the management of memory deficit disorders like AD.
ESTHER : Ayaz_2017_Front.Pharmacol_8_697
PubMedSearch : Ayaz_2017_Front.Pharmacol_8_697
PubMedID: 29056913

Title : Mutations in the lipase-H gene causing autosomal recessive hypotrichosis and woolly hair - Mehmood_2015_Australas.J.Dermatol_56_e66
Author(s) : Mehmood S , Jan A , Muhammad D , Ahmad F , Mir H , Younus M , Ali G , Ayub M , Ansar M , Ahmad W
Ref : Australas J Dermatol , 56 :e66 , 2015
Abstract : Hypotrichosis is characterised by sparse scalp hair, sparse to absent eyebrows and eyelashes, or absence of hair from other parts of the body. In few cases, the condition is associated with tightly curled woolly scalp hair. The present study searched for disease-causing sequence variants in the genes in four Pakistani lineal consanguineous families exhibiting features of hypotrichosis or woolly hair. A haplotype analysis established links in all four families to the LIPH gene located on chromosome 3q27.2. Subsequently, sequencing LIPH identified a novel non-sense mutation (c.328C>T; p.Arg110*) in one and a previously reported 2-bp deletion mutation (c.659_660delTA, p.Ile220ArgfsX29) in three other families.
ESTHER : Mehmood_2015_Australas.J.Dermatol_56_e66
PubMedSearch : Mehmood_2015_Australas.J.Dermatol_56_e66
PubMedID: 24628704
Gene_locus related to this paper: human-LIPH

Title : Mutations in the LPAR6 and LIPH genes underlie autosomal recessive hypotrichosis\/woolly hair in 17 consanguineous families from Pakistan - Khan_2011_Clin.Exp.Dermatol_36_652
Author(s) : Khan S , Habib R , Mir H , Umm e K , Naz G , Ayub M , Shafique S , Yamin T , Ali N , Basit S , Wasif N , Kamran-ul-Hassan Naqvi S , Ali G , Wali A , Ansar M , Ahmad W
Ref : Clinical & Experimental Dermatologyatol , 36 :652 , 2011
Abstract : BACKGROUND: Autosomal recessive hypotrichosis/woolly hair is a rare genetic hair loss disorder characterized by sparse scalp hair/woolly hair, sparse to absent eyebrows and eyelashes, sparse axillary and body hair in affected individuals. This form of hair loss results from mutations in either LPAR6 or LIPH gene. AIM: To identify mutations in LPAR6 and LIPH genes in 17 consanguineous Pakistani families showing features of hypotrichosis/woolly hair. METHODS: Genotyping in 17 families was carried out using polymorphic microsatellite markers linked to genes causing autosomal recessive hypotrichosis/woolly hair phenotype. To screen for mutations in LPAR6 and LIPH genes, all of their exons and splice junction sites were amplified by PCR and sequenced using an automated DNA sequencer. RESULTS: Genotyping with polymorphic microsatellite markers showed linkage in eight families to LPAR6 and in nine families to LIPH gene. Sequence analysis revealed four recurrent mutations (p.Phe24HisfsX28; p.Asp63Val; p.Gly146Arg; p.Ile188Phe) in LPAR6 and two recurrent mutations (p.Trp108Arg; p.Ile220ArgfsX29) in LIPH gene. Comparison of the haplotypes generated by typing LPAR6 and LIPH genes linked microsatellite markers in different families suggested common founder natures of the two mutations (c.66_69insCATG and c.659_660delTA). CONCLUSIONS: Mutations identified in the present study extend the body of evidence implicating LPAR6 and LIPH genes in pathogenesis of human hereditary hair loss.
ESTHER : Khan_2011_Clin.Exp.Dermatol_36_652
PubMedSearch : Khan_2011_Clin.Exp.Dermatol_36_652
PubMedID: 21426374
Gene_locus related to this paper: human-LIPH

Title : Genetic mapping of a novel hypotrichosis locus to chromosome 7p21.3-p22.3 in a Pakistani family and screening of the candidate genes - Basit_2010_Hum.Genet_128_213
Author(s) : Basit S , Ali G , Wasif N , Ansar M , Ahmad W
Ref : Hum Genet , 128 :213 , 2010
Abstract : Hereditary hypotrichosis is a heterogeneous group of inherited hair loss disorders characterized by diffused or localized thinning or absence of hair affecting scalp, eyebrows and eyelashes, and other body parts. Over the past few years, at least four autosomal dominant and six autosomal recessive forms of hypotrichosis have been described. All these ten forms of hypotrichosis have been mapped on different human chromosomes and the corresponding genes have been identified in most of these cases. In the present study, we have described a six-generation Pakistani consanguineous family with an autosomal recessive transmission of hereditary hypotrichosis. All the five affected individuals of the family showed complete absence of scalp hair and sparse eyebrows and eyelashes. They were born with complete absence of scalp hairs. Facial hair of beard and mustaches were present in all the affected adult male individuals. Papules were observed only on scalp of the affected individuals. A scalp biopsy from an affected individual showed markedly reduced number of hair follicles. Human genome scan using polymorphic microsatellite markers mapped the disease locus on chromosome 7p21.3-p22.3, flanked by markers D7S1532 and D7S3047. A maximum two-point LOD score of 4.74 (theta = 0.00) was obtained at marker D7S481. The linkage interval spans 15.69 cM, which corresponds to 6.59 Mb according to the sequence-based physical map (Build 36.2). Mutation analysis of five potential candidate genes (GNA12, FOXK1, DAGLB, ZNF12, ACTB), located in the linkage interval, did not reveal any functional sequence variant.
ESTHER : Basit_2010_Hum.Genet_128_213
PubMedSearch : Basit_2010_Hum.Genet_128_213
PubMedID: 20544222

Title : Mutations in lipase H gene underlie autosomal recessive hypotrichosis in five Pakistani families -
Author(s) : Kalsoom UE , Habib R , Khan B , Ali G , Ali N , Ansar M , Ahmad W
Ref : Acta Derm Venereol , 90 :93 , 2010
PubMedID: 20107739
Gene_locus related to this paper: human-LIPH

Title : Novel missense mutations in lipase H (LIPH) gene causing autosomal recessive hypotrichosis (LAH2) - Naz_2009_J.Dermatol.Sci_54_12
Author(s) : Naz G , Khan B , Ali G , Azeem Z , Wali A , Ansar M , Ahmad W
Ref : J Dermatol Sci , 54 :12 , 2009
Abstract : BACKGROUND: Autosomal recessive hypotrishosis (LAH2) is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. However, affected male individuals have normal beard hair. Mutations in lipase H (LIPH) gene, located on chromosome 3q26.33, have been shown to be responsible for LAH2 type of hypotrichosis. OBJECTIVES: To search for pathogenic mutations in LIPH gene at LAH2 locus in Pakistani families demonstrating autosomal recessive hypotrichosis. METHODS: In the present study we have ascertained two large unrelated consanguineous Pakistani families (A and B) inherited autosomal recessive form of hypotrichosis. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene at LAH2 locus on chromosome 3q26.33. These families were then subjected to direct sequencing of the LIPH gene. RESULTS: Sequence analysis of the LIPH gene revealed two novel missense mutations (c.2T>C; p.M1T and c.322T>C; p.W108R) in the two families. CONCLUSION: The mutations reported here are the first missense mutations identified in the LIPH gene, which extend the body of evidences implicating the LIPH gene in the pathogenesis of human hereditary hair loss.
ESTHER : Naz_2009_J.Dermatol.Sci_54_12
PubMedSearch : Naz_2009_J.Dermatol.Sci_54_12
PubMedID: 19167195
Gene_locus related to this paper: human-LIPH

Title : A novel deletion mutation in LIPH gene causes autosomal recessive hypotrichosis (LAH2) - Jelani_2008_Clin.Genet_74_184
Author(s) : Jelani M , Wasif N , Ali G , Chishti M , Ahmad W
Ref : Clin Genet , 74 :184 , 2008
Abstract : Autosomal recessive hypotrichosis is a rare hereditary disorder characterized by sparse hair on scalp and rest of the body of affected subjects. Recently, three clinically similar autosomal recessive forms of hypotrichosis [localized autosomal recessive hypotrichosis (LAH)1], LAH2 and LAH3 have been mapped on chromosomes 18q12.1, 3q27.3, and 13q14.11-q21.32, respectively. For these three loci, two genes DSG4 for LAH1 and LIPH for LAH2 have been identified. To date, only five mutations in DSG4 and two in LIPH genes have been reported. In this study, we have ascertained two large unrelated consanguineous Pakistani families with autosomal recessive form of hypotrichosis. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene on chromosome 3q27. Sequence analysis of the gene in the affected subjects from both the families revealed a novel deletion mutation in exon 5 (c.659-660delTA) causing frameshift and downstream premature termination codon. All the three mutations identified in the LIPH gene, including the one in this study, are deletion mutations.
ESTHER : Jelani_2008_Clin.Genet_74_184
PubMedSearch : Jelani_2008_Clin.Genet_74_184
PubMedID: 18445047
Gene_locus related to this paper: human-LIPH

Title : A mutation in the lipase H (LIPH) gene underlie autosomal recessive hypotrichosis - Ali_2007_Hum.Genet_121_319
Author(s) : Ali G , Chishti MS , Raza SI , John P , Ahmad W
Ref : Hum Genet , 121 :319 , 2007
Abstract : Hereditary hypotrichosis is a rare autosomal recessive disorder characterized by sparse hair on scalp and rest of the body of affected individuals. Two forms of such hypotrichosis LAH and AH have been mapped on chromosome 18q12.1 and 3q27, respectively. Mutations in desmogelin 4 (DSG4) gene have been reported to underlie LAH. Recently, a deletion mutation in Lipase H (LIPH) gene, located at AH locus, has been identified in two ethnic groups of Russian population. In the present study, a four generation Pakistani family with AH phenotype has been mapped to chromosome 3q27. Sequence analysis of candidate gene LIPH revealed a novel five base pair deletion mutation (c.346-350delATATA) in exon 2 of the gene leading to frameshift and downstream premature termination codon. The mutation reported in the family, presented here, is the second mutation identified in LIPH gene. The identification of a genetic defect in LIPH suggests that this enzyme regulates hair growth.
ESTHER : Ali_2007_Hum.Genet_121_319
PubMedSearch : Ali_2007_Hum.Genet_121_319
PubMedID: 17333281
Gene_locus related to this paper: human-LIPH