Full Text Journal Articles by
Author Khaled S Abd Elrahman

Advertisement

Find full text journal articles






A M1 muscarinic acetylcholine receptor positive allosteric modulator improves pathology and cognitive deficits in female APPswe/PSEN1ΔE9 mice.

Khaled S Abd-Elrahman, Shaarika Sarasija, Tash-Lynn L Colson, Stephen S G Ferguson,

<h4>Background and purpose</h4>Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline and women account for 60% of diagnosed cases. Beta-amyloid (Aβ) oligomers is considered the principal neurotoxic species in AD brains. The M1 muscarinic acetylcholine receptor (M1 mAChR) plays a key role in memory and learning. M1 ... Read more >>

Br J Pharmacol (British journal of pharmacology)
[2021, :]

Cited: 0 times

View full text PDF listing >>



The role of neuroglial metabotropic glutamate receptors in Alzheimer's disease.

Khaled S Abd-Elrahman, Shaarika Sarasija, Stephen S G Ferguson,

Glutamate, the major excitatory neurotramitter in the brain exerts its effects via both ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). There are three subgroups of mGluRs, pre-synaptic Group II and Group III mGluRs and post-synaptic Group I mGluRs. mGluRs are ubiquitously expressed in the brain and their activation is ... Read more >>

Curr Neuropharmacol (Current neuropharmacology)
[2021, :]

Cited: 0 times

View full text PDF listing >>



Advertisement

Metabotropic Glutamate Receptor 2/3 Activation Improves Motor Performance and Reduces Pathology in Heterozygous zQ175 Huntington Disease Mice.

Si Han Li, Tash-Lynn L Colson, Khaled S Abd-Elrahman, Stephen S G Ferguson,

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that leads to progressive motor impairments with no available disease-modifying treatment. Current evidence indicates that exacerbated postsynaptic glutamate signaling in the striatum plays a key role in the pathophysiology of HD. However, it remains unclear whether reducing glutamate release can be ... Read more >>

J Pharmacol Exp Ther (The Journal of pharmacology and experimental therapeutics)
[2021, 379(1):74-84]

Cited: 0 times

View full text PDF listing >>



Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease.

Khaled S Abd-Elrahman, Stephen S G Ferguson,

Metabotropic glutamate receptor 5 (mGluR5) is ubiquitously expressed in brain regions responsible for memory and learning. It plays a key role in modulating rapid changes in synaptic transmission and plasticity. mGluR5 supports long-term changes in synaptic strength by regulating the transcription and translation of essential synaptic proteins. β-Amyloid 42 (Aβ42) ... Read more >>

Annu Rev Pharmacol Toxicol (Annual review of pharmacology and toxicology)
[2021, :]

Cited: 0 times

View full text PDF listing >>



The pleiotropic effects of antithrombotic drugs in the metabolic-cardiovascular-neurodegenerative disease continuum: impact beyond reduced clotting.

Rana A Alaaeddine, Ibrahim AlZaim, Safaa H Hammoud, Aya Arakji, Ali H Eid, Khaled S Abd-Elrahman, Ahmed F El-Yazbi,

Antithrombotic drugs are widely used for primary and secondary prevention, as well as treatment of many cardiovascular disorders. Over the past few decades, major advances in the pharmacology of these agents have been made with the introduction of new drug classes as novel therapeutic options. Accumulating evidence indicates that the ... Read more >>

Clin Sci (Lond) (Clinical science (London, England : 1979))
[2021, 135(8):1015-1051]

Cited: 0 times

View full text PDF listing >>



Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner.

Khaled S Abd-Elrahman, Awatif Albaker, Jessica M de Souza, Fabiola M Ribeiro, Michael G Schlossmacher, Mario Tiberi, Alison Hamilton, Stephen S G Ferguson,

The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits distinct sex-dependent profiles. Specifically, ... Read more >>

Sci Signal (Science signaling)
[2020, 13(662):]

Cited: 3 times

View full text PDF listing >>



Optineurin deletion disrupts metabotropic glutamate receptor 5-mediated regulation of ERK1/2, GSK3β/ZBTB16, mTOR/ULK1 signaling in autophagy.

Karim S Ibrahim, Caitlyn J McLaren, Khaled S Abd-Elrahman, Stephen S G Ferguson,

Optineurin (OPTN) is a multifunctional protein that mediates a network of cellular processes regulating membrane trafficking, inflammatory responses and autophagy. The OPTN-rich interactome includes Group I metabotropic glutamate receptors (mGluR1 and 5), members of the Gα<sub>q/11</sub> protein receptor family. Recent evidence has shown that mGluR5, in addition to its canonical ... Read more >>

Biochem Pharmacol (Biochemical pharmacology)
[2021, 185:114427]

Cited: 0 times

View full text PDF listing >>



mGluR5 regulates REST/NRSF signaling through N-cadherin/β-catenin complex in Huntington's disease.

Jéssica M de Souza, Khaled S Abd-Elrahman, Fabiola M Ribeiro, Stephen S G Ferguson,

Repressor element 1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a transcription repressor and its expression is regulated by the Wnt pathway through β-catenin. Metabotropic glutamate receptor 5 (mGluR5) signaling plays a key role in controlling neuronal gene expression. Interestingly, REST/NRSF nuclear translocation and signaling, as well as mGluR5 signaling are ... Read more >>

Mol Brain (Molecular brain)
[2020, 13(1):118]

Cited: 0 times

View full text PDF listing >>



Targeting Vesicular Glutamate Transporter Machinery: Implications on Metabotropic Glutamate Receptor 5 Signaling and Behavior.

Karim S Ibrahim, Khaled S Abd-Elrahman, Salah El Mestikawy, Stephen S G Ferguson,

Cross talk between both pre- and postsynaptic components of glutamatergic neurotransmission plays a crucial role in orchestrating a multitude of brain functions, including synaptic plasticity and motor planning. Metabotropic glutamate receptor (mGluR) 5 exhibits promising therapeutic potential for many neurodevelopmental and neurodegenerative disorders as a consequence of its modulatory control ... Read more >>

Mol Pharmacol (Molecular pharmacology)
[2020, 98(4):314-327]

Cited: 3 times

View full text PDF listing >>



mGluR5 Contribution to Neuropathology in Alzheimer Mice Is Disease Stage-Dependent.

Khaled S Abd-Elrahman, Alison Hamilton, Awatif Albaker, Stephen S G Ferguson,

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and is characterized by a progressive cognitive decline in affected individuals. Current therapeutic strategies are limited in their efficacy and some have proven to be even less effective at later disease stages or after extended use. We previously demonstrated that chronic ... Read more >>

ACS Pharmacol Transl Sci (ACS pharmacology & translational science)
[2020, 3(2):334-344]

Cited: 5 times

View full text PDF listing >>



Structural determinants governing β-arrestin2 interaction with PDZ proteins and recruitment to CRFR1.

Sarah Gupta, Khaled S Abd-Elrahman, Awatif Albaker, Henry A Dunn, Stephen S G Ferguson,

β-Arrestins are multifunctional adaptor proteins best know for their vital role in regulating G protein coupled receptor (GPCR) trafficking and signaling. β-arrestin2 recruitment and receptor internalization of corticotropin-releasing factor receptor 1 (CRFR1), a GPCR whose antagonists have been shown to demonstrate both anxiolytic- and antidepressant-like effects, have previously been shown ... Read more >>

Cell Signal (Cellular signalling)
[2019, 63:109361]

Cited: 2 times

View full text PDF listing >>



mGluR5 Allosteric Modulation Promotes Neurorecovery in a 6-OHDA-Toxicant Model of Parkinson's Disease.

Kyle Farmer, Khaled S Abd-Elrahman, Alexa Derksen, Elyn M Rowe, Ashley M Thompson, Christopher A Rudyk, Natalie A Prowse, Zachary Dwyer, Samantha C Bureau, Teresa Fortin, Stephen S G Ferguson, Shawn Hayley,

Parkinson's disease is a neurodegenerative disease characterized by a loss of dopaminergic substantia nigra neurons and depletion of dopamine. To date, current therapeutic approaches focus on managing motor symptoms and trying to slow neurodegeneration, with minimal capacity to promote neurorecovery. mGluR5 plays a key role in neuroplasticity, and altered mGluR5 ... Read more >>

Mol Neurobiol (Molecular neurobiology)
[2020, 57(3):1418-1431]

Cited: 3 times

View full text PDF listing >>



Amelioration of perivascular adipose inflammation reverses vascular dysfunction in a model of nonobese prediabetic metabolic challenge: potential role of antidiabetic drugs.

Mohammed A W Elkhatib, Ali Mroueh, Rim W Rafeh, Fatima Sleiman, Hosny Fouad, Evan I Saad, Mohamed A Fouda, Ola Elgaddar, Khodr Issa, Ali H Eid, Assaad A Eid, Khaled S Abd-Elrahman, Ahmed F El-Yazbi,

The onset of vascular impairment precedes that of diagnostic hyperglycemia in diabetic patients suggesting a vascular insult early in the course of metabolic dysfunction without a well-defined mechanism. Mounting evidence implicates adipose inflammation in the pathogenesis of insulin resistance and diabetes. It is not certain whether amelioration of adipose inflammation ... Read more >>

Transl Res (Translational research : the journal of laboratory and clinical medicine)
[2019, 214:121-143]

Cited: 4 times

View full text PDF listing >>



Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington's pathology in zQ175 mice.

Khaled S Abd-Elrahman, Stephen S G Ferguson,

Huntington's disease (HD) is a neurodegenerative disorder caused by a genetic abnormality in the huntingtin gene that leads to a polyglutamine repeat expansion of the huntingtin protein. The cleaved polyglutamine expansion of mutant huntingtin (mHTT) protein can form aggregates strongly correlated with HD progression. We have previously shown that the ... Read more >>

Mol Brain (Molecular brain)
[2019, 12(1):35]

Cited: 12 times

View full text PDF listing >>



GRK2 knockdown in mice exacerbates kidney injury and alters renal mechanisms of blood pressure regulation.

Elena Tutunea-Fatan, Khaled S Abd-Elrahman, Jean-Francois Thibodeau, Chet E Holterman, Brian J Holleran, Richard Leduc, Christopher R J Kennedy, Robert Gros, Stephen S G Ferguson,

The renin-angiotensin system regulates blood pressure and fluid balance in the body primarily via angiotensin receptor 1 (AT1R). Renal AT1R was found to be primarily responsible for Ang II-mediated hypertension. G protein-coupled receptor kinase 2 (GRK2) modulates AT1R desensitization and increased GRK2 protein expression is reported in hypertensive patients. However, ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):11415]

Cited: 4 times

View full text PDF listing >>



Podocyte NADPH Oxidase 5 Promotes Renal Inflammation Regulated by the Toll-Like Receptor Pathway.

Chet E Holterman, Naomi C Boisvert, Jean-François Thibodeau, Eldjonai Kamto, Melica Novakovic, Khaled S Abd-Elrahman, Stephen S G Ferguson, Christopher R J Kennedy,

<h4>Aims</h4>Oxidative stress associated with a proinflammatory state occurs in endothelial dysfunction, hypertension, chronic kidney disease, and diabetes. The NADPH oxidase (Nox) family of reactive oxygen species (ROS) generating enzymes is implicated in these processes, yet little information regarding the role of Nox5 is available. Our aim was to investigate the ... Read more >>

Antioxid Redox Signal (Antioxidants & redox signaling)
[2019, 30(15):1817-1830]

Cited: 8 times

View full text PDF listing >>



Autophagy is increased following either pharmacological or genetic silencing of mGluR5 signaling in Alzheimer's disease mouse models.

Khaled S Abd-Elrahman, Alison Hamilton, Maryam Vasefi, Stephen S G Ferguson,

Alzheimer's disease (AD) is characterized by neurotoxicity mediated by the accumulation of beta amyloid (Aβ) oligomers, causing neuronal loss and progressive cognitive decline. Genetic deletion or chronic pharmacological inhibition of mGluR5 by the negative allosteric modulator CTEP, rescues cognitive function and reduces Aβ aggregation in both APPswe/PS1ΔE9 and 3xTg-AD mouse ... Read more >>

Mol Brain (Molecular brain)
[2018, 11(1):19]

Cited: 9 times

View full text PDF listing >>



mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington's disease.

Khaled S Abd-Elrahman, Alison Hamilton, Shaunessy R Hutchinson, Fang Liu, Ryan C Russell, Stephen S G Ferguson,

Huntington's disease (HD) is a neurodegenerative disease caused by an expansion in the huntingtin protein (also called Htt) that induces neuronal cell death with age. We found that the treatment of 12-month-old symptomatic heterozygous and homozygous zQ175 huntingtin knockin mice for 12 weeks with CTEP, a negative allosteric modulator of ... Read more >>

Sci Signal (Science signaling)
[2017, 10(510):]

Cited: 14 times

View full text PDF listing >>



ROK and Arteriolar Myogenic Tone Generation: Molecular Evidence in Health and Disease.

Ahmed F El-Yazbi, Khaled S Abd-Elrahman,

The myogenic response is an inherent property of resistance arteries that warrants a relatively constant blood flow in response to changes in perfusion pressure and protect delicate organs from vascular insufficiencies and excessive blood flow. This fundamental phenomenon has been extensively studied aiming to elucidate the underlying mechanisms triggering smooth ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2017, 8:87]

Cited: 3 times

View full text PDF listing >>



Abnormal myosin phosphatase targeting subunit 1 phosphorylation and actin polymerization contribute to impaired myogenic regulation of cerebral arterial diameter in the type 2 diabetic Goto-Kakizaki rat.

Khaled S Abd-Elrahman, Olaia Colinas, Emma J Walsh, Hai-Lei Zhu, Christine M Campbell, Michael P Walsh, William C Cole,

The myogenic response of cerebral resistance arterial smooth muscle to intraluminal pressure elevation is a key physiological mechanism regulating blood flow to the brain. Rho-associated kinase plays a critical role in the myogenic response by activating Ca<sup>2+</sup> sensitization mechanisms: (i) Rho-associated kinase inhibits myosin light chain phosphatase by phosphorylating its ... Read more >>

J Cereb Blood Flow Metab (Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism)
[2017, 37(1):227-240]

Cited: 8 times

View full text PDF listing >>



Vascular Smooth Muscle-Specific EP4 Receptor Deletion in Mice Exacerbates Angiotensin II-Induced Renal Injury.

Jean-Francois Thibodeau, Chet E Holterman, Ying He, Anthony Carter, Gregory O Cron, Naomi C Boisvert, Khaled S Abd-Elrahman, Karolynn J Hsu, Stephen S G Ferguson, Christopher R J Kennedy,

<h4>Aims</h4>Cyclooxygenase inhibition by non-steroidal anti-inflammatory drugs is contraindicated in hypertension, as it may reduce glomerular filtration rate (GFR) and renal blood flow. However, the identity of the specific eicosanoid and receptor underlying these effects is not known. We hypothesized that vascular smooth muscle prostaglandin E2 (PGE2) E-prostanoid 4 (EP4) receptor ... Read more >>

Antioxid Redox Signal (Antioxidants & redox signaling)
[2016, 25(12):642-656]

Cited: 5 times

View full text PDF listing >>



PKC-mediated cerebral vasoconstriction: Role of myosin light chain phosphorylation versus actin cytoskeleton reorganization.

Ahmed F El-Yazbi, Khaled S Abd-Elrahman, Alejandro Moreno-Dominguez,

Defective protein kinase C (PKC) signaling has been suggested to contribute to abnormal vascular contraction in disease conditions including hypertension and diabetes. Our previous work on agonist and pressure-induced cerebral vasoconstriction implicated PKC as a major contributor to force production in a myosin light chain (LC20) phosphorylation-independent manner. Here, we ... Read more >>

Biochem Pharmacol (Biochemical pharmacology)
[2015, 95(4):263-278]

Cited: 18 times

View full text PDF listing >>



Abnormal Rho-associated kinase activity contributes to the dysfunctional myogenic response of cerebral arteries in type 2 diabetes.

Khaled S Abd-Elrahman, Michael P Walsh, William C Cole,

The structural and functional integrity of the brain, and therefore, cognition, are critically dependent on the appropriate control of blood flow within the cerebral circulation. Inadequate flow leads to ischemia, whereas excessive flow causes small vessel rupture and (or) blood-brain-barrier disruption. Cerebral blood flow is controlled through the interplay of ... Read more >>

Can J Physiol Pharmacol (Canadian journal of physiology and pharmacology)
[2015, 93(3):177-184]

Cited: 10 times

View full text PDF listing >>



PPARγ dependence of cyclosporine-isoprenaline renovascular interaction: roles of nitric oxide synthase and heme oxygenase.

Hanan M El-Gowelli, Khaled S Abd-Elrahman, Evan I Saad, Sahar M El-Gowilly, Abdel-Galil A Abdel-Galil, Mahmoud M El-Mas,

We previously showed that cyclosporine (CSA) impairs renal vasodilations caused by β-adrenoceptor activation. This study investigated whether the peroxisome proliferator-activated receptor gamma (PPARγ) and related nitric oxide synthase (NOS)/heme oxygenase (HO) signaling mediates the CSA-β-adrenoceptor interaction. The vasodilatory response elicited by a bolus injection of isoprenaline (1 μmole) in phenylephrine-preconstricted ... Read more >>

J Cardiovasc Pharmacol (Journal of cardiovascular pharmacology)
[2011, 58(2):173-180]

Cited: 6 times

View full text PDF listing >>



Stromatoxin-sensitive, heteromultimeric Kv2.1/Kv9.3 channels contribute to myogenic control of cerebral arterial diameter.

Xi Zoë Zhong, Khaled S Abd-Elrahman, Chiu-Hsiang Liao, Ahmed F El-Yazbi, Emma J Walsh, Michael P Walsh, William C Cole,

Cerebral vascular smooth muscle contractility plays a crucial role in controlling arterial diameter and, thereby, blood flow regulation in the brain. A number of K(+) channels have been suggested to contribute to the regulation of diameter by controlling smooth muscle membrane potential (E(m)) and Ca(2+) influx. Previous studies indicate that ... Read more >>

J Physiol (The Journal of physiology)
[2010, 588(Pt 22):4519-4537]

Cited: 37 times

View full text PDF listing >>



Advertisement


Disclaimer

1.299 s