China
Africa
Explore chapters and articles related to this topic
Molecular Drivers in Lung Adenocarcinoma: Therapeutic Implications
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Imayavaramban Lakshmanan, Apar Kishor Ganti
KRAS is a member of the Ras family that promotes cell growth and division. This pathway is activated by the binding of guanosine triphosphate (GTP) and phosphorylates downstream signaling proteins. The process continues until the GTP is converted to guanosine diphosphate (GDP) through an intrinsic GTPase activity that is present in the Ras family enzymes. While the Ras family includes both HRAS and NRAS, in addition to KRAS, KRAS alone has been implicated in the lung carcinogenesis.
Developmental Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James H. Tonsgard, Nikolas Mata-Machado
SW is due to a somatic mutation in the GNAQ gene in skin and meninges. GNAQ encodes Gaq, a member of the G-protein α subunits that mediate signals between G-protein–coupled receptors and downstream effectors. The mutation results in a reduction in GTPase activity leading to increased signaling activity. It is postulated that dysregulation through G-protein–coupled receptors such as that for endothelin may result in malformed progressively dilated blood vessels, a developmental abnormality of the embryonic vascular plexus in the cephalic mesenchyme adjacent to the telencephalic vesicle. It is hypothesized that there is an abnormal regulation of blood vessels, and extracellular matrix expression that produces tortuous abnormal blood vessels in the leptomeninges with sluggish blood flow results in progressive ischemia to the underlying cortex.19
Dopamine Receptors, Signaling Pathways, and Drugs
Published in Nira Ben-Jonathan, Dopamine, 2020
The G proteins belong to a large group of enzymes that function as GTPases. When bound to GTP, G proteins are in an “on,” active conformation, whereas when bound to GDP, they are at an “off,” inactive state [7,8]. The extent of G protein activation by the GPCRs is usually proportional to the concentration of the bound ligand. Within the brain, the GPCRs act primarily, but not exclusively, as mediators of slow neuromodulators rather than fast neurotransmitters [7]. The GPCRs mediate a large variety of neurological events, among which are the chemosensory recognition systems (vision, olfaction, taste), movement regulation, and complex behavioral events. In the periphery, GPCRs mediate the actions of many paracrine peptides and circulating hormones, serving as an integral component of endocrine regulation. In the immune system, GPCRs participate in the control of lymphocyte trafficking and motility and are involved in T-cell activation. There are over 160 orphan GPCRs whose natural ligands are still unknown.
Clinical significance of serum CDC42 in the prediction of uremic vascular calcification incidence and progression
Published in Libyan Journal of Medicine, 2023
Mingzhi Xu, Mingjiao Pan, Na An, Ruman Chen, Yafei Bai, Jiqing He, Chunli Wang, Yonghui Qi
The Rho family of GTPases emerges as vital molecules that tune-fine the structures and functions of kidney cell types, thus affecting kidney physiology and diseases [8]. Cell division cycle 42 (CDC42), one of the best characterized members of the Rho family of GTPases, plays a role in the regulation of various cell functions, such as cytoskeletal architecture, polarity, cytokinesis, proliferation, and migration [9–12]. Depletion of CDC42 triggers injury of vascular endothelial cells and inhibits vascular endothelial growth factor A-mediated vascular sprouting from aortic rings, contributing to the defect in vasculature formation of various organs [13]. Meanwhile, CDC42 modulates epithelial cell polarity and the actin cytoskeleton to participate in kidney epithelial tubulogenesis [14]. The deficiency of CDC42 results in a disruption of renal ciliogenesis and a polycystic kidney disease phenotype in zebrafish and mice [15]. The role of CDC42 in cartilage development and calcified tissue formation has also been reported [16]. Most importantly, the recruitment of CDC42 promotes VC in the context of CKD by upregulating the expression of bone-related factors [17]. However, the role and expression patterns of CDC42 in uremia have not been discussed before.
Rational design, optimization, and biological evaluation of novel α-Phosphonopropionic acids as covalent inhibitors of Rab geranylgeranyl transferase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Joanna Małolepsza, Aleksandra Marchwicka, Remigiusz A. Serwa, Sanna P. Niinivehmas, Olli T. Pentikäinen, Edyta Gendaszewska-Darmach, Katarzyna M. Błażewska
Encouraged by the possible benefits of this approach, we designed first covalent inhibitors of Rab geranylgeranyltransferase, derived from α-phosphonocarboxylates (PCs). RGGT is involved in the post-translational modification of eukaryotic Rab GTPases, the primary regulators of the formation, transport, docking, and fusion of vesicles during membrane transport.8 The dysfunction of Rab GTPases leads to various diseases ranging from infections to cancer.9 RGGT catalyses double prenylation of most Rab GTPases, with the formation of a thioether bond between two C-terminal cysteines and isoprenoid chains derived from geranylgeranyl pyrophosphate. This modification is necessary for the proper functioning of Rab GTPases, making RGGT a potential drug target. RGGT is a heterodimer composed of an α subunit encoded by the RABGGTA gene and a β subunit encoded by the RABGGTB gene.10
Therapeutic effect of statins on airway remodeling during asthma
Published in Expert Review of Respiratory Medicine, 2022
Mashael Alabed, Noha Mousaad Elemam, Rakhee K Ramakrishnan, Narjes Saheb Sharif-Askari, Tarek Kashour, Qutayba Hamid, Rabih Halwani
Statins are considerably one of the most efficient lipid-lowering medications. Their main mechanism of action is through the inhibition of the enzyme β-hydroxy β-methylglutaryl- coenzyme A (HMG-CoA) reductase, which controls the rate-limiting step in the synthesis of cholesterol. Statins inhibit the conversion of HMG-CoA to mevalonate via the mevalonate pathway. This will lead to a decrease in mevalonate’s metabolites including isoprenoids, such as isopentenyl diphosphate (IPP), farnesyl pyrophosphate (FPP), geranylgeranyl pyrophosphate (GGPP), and sterols, such as squalene and cholesterol. Isoprenoids represent crucial players in the regulation of small GTPases of the Rab, Rho, and Ras families. GTPases are recognized as key molecules that play a role in cell survival, proliferation, differentiation, and immune system regulation [32–34].