Signal transduction

Lead Identification (LO): Lead compounds bind to target receptors, and shows potentially therapeutic pharmacological activity, and may contain similar structures and functional groups. Lead compounds are used as a foundation for drug development and may be modified structurally for greater pharmacodynamic efficiency and potency.1 One source of determining lead compounds is by assaying libraries through HTS. Researchers analyze the drug’s ADME properties (Absorption, Distribution, Metabolism, and…

Downstream Targets Due to the lack of developing an effective Ras treatment, some have turned to targeting downstream effectors of Ras. Downstream effectors have a critical role in Ras carcinogenesis and are commonly found in KRAS mutated cancers. The most intensely targeted pathways are the Raf-MEK-ERK (MAPK) and PI3K-AKT-mTOR signaling pathways. Raf-MEK-ERK MAPK signaling is initiated through receptor tyrosine kinases after their activation by growth factors (Mccubrey 2006). Once Ras is in its…

Receptors are protein molecules that receive chemical signals in the form of ligands and induce responses at cellular level. They are localized at the cell surface, cytoplasm or the nucleus, depending on their amino acid sequences. In addition to using these three different localizations to categorize receptors, the types of action of receptors are also used as a mean of classification. The four main classifications of receptors are: 1. Ionotropic (or ligand-gated ion channel) receptors, 2.…

According to T.F. Gendron et al., partial amounts of the toxicity are due to a gain in function by the protein. When this occurs, the TDP-43 protein has usually shifted its location from the nucleus to throughout the cytoplasm of the cell. This abnormal accumulation of TDP-43 in the cytoplasm is not only found in neurons and glial cells of the primary motor cortex but as well as in brainstem motor nuclei, the spinal cord, and in certain associated white matter tracts (Mackenzie et al 2010). It…

proteins like NSF, SNAPs (soluble NSF attachment proteins), and SNAREs including SNAP25, VAMP and syntaxin. With these identified proteins, Rothman laboratory developed the SNARE hypothesis describing a model of SNAREs involvement in vesicle targeting and fusion. Their model explains that a transport vesicle (v-SNARE) and a target membrane (t-SNARE) with the aid of NSF, SNAPs and other yet unknown proteins bring the v-SNARE in close proximity to the t-SNARE facilitating membrane fusion (Sollner…

(1-AR) are systematic vasoconstrictors: their activation constricts blood vessels by the contraction of vascular smooth muscle. These transmembrane receptors are activated by the binding of epinephrine or norepinephrine, which creates intracellular signals via activation of the G-protein. The G-protein itself is a heterotrimer; it consists of alpha, beta, and gamma subunits (Figure 1). The alpha subunit of the G-protein is capable of binding to guanosine diphosphate (GDP) or guanosine…

Hypothalamic programming of systemic ageing involving IKK-b, NF-kB and GnRH (Zhang et al., 2013). Cellular senescence is when a cell’s replicative mechanism becomes arrested. This was phenomenon was first described in Hayflick’s experiment. Cellular senescence is usually due to protect the cell from becoming cancerous but it also plays a prominent role in aging (van Deursen, 2014). While senescence describes a halt in proliferation, cancer development is the uncontrolled proliferation of…

then reassemble. This will cause the cycle to end as the G-Protein is now again in its inactive heterotrimeric, GDP bound state. Once the G-Protein has left the receptor, the receptor can then go onto activate other nearby G-Proteins. This leads to signal amplification as the receptor, when bound to an agonist, can activate multiple…

Calcium is the richest mineral in our body holding many functions during the human development. Ca2+ controls many cellular processes such as: metabolism, gene transcription, fertilisation, proliferation, hypertrophy, secretion, exocytosis, cardiac ventricular mechanisms, neuronal dopaminergic pacemaker mechanisms, contraction, coordination and thinking, (Rubin, 2016). These processes can occur anywhere between a few microseconds to hours to complete. The basal Ca2+ concentration of…

Kaempferol is a natural polyphenol, secondary metabolite (flavonol), a type of flavonoid, found in a variety of plant-derived foods. Kaempferol is a yellow crystalline solid with a melting point of 276–278 °C. It is slightly soluble in water and highly soluble in hot ethanol, ethers, and DMSO. Kaempferol acts as an antioxidant by reducing oxidative stress. Many studies suggest that consuming kaempferol may reduce the risk of various cancers, and it is currently under consideration as a possible…