Our fusion protein, TP1_P5 incorporated multiple signaling pathways to tackle CVDs, specifically atherosclerosis and thrombosis
By activating the phosphoinositide 3-kinase (PI3K)-Akt pathway, Ginsentide TP1 enhances nitric oxide (NO) production and modulates various cellular processes that contribute to cardiovascular health. This exploration delves deeper into how Ginsentide TP1 influences vascular dynamics, focusing on nitric oxide signaling, smooth muscle relaxation, and its role in platelet aggregation.
Upon administration, Ginsentide TP1 activates the PI3K-Akt signaling pathway, which is pivotal in various cellular responses. This pathway is crucial for promoting cell survival, growth, and metabolism. The activation of PI3K leads to the phosphorylation of Akt, a serine/threonine kinase that further stimulates endothelial nitric oxide synthase (eNOS).
The activation of eNOS results in the production of nitric oxide (NO) from L-arginine. NO is a signaling molecule that diffuses from endothelial cells into adjacent smooth muscle cells, where it exerts significant effects. Once inside these cells, NO activates guanylate cyclase, an enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP).
cGMP serves as a second messenger in various physiological processes. One of its primary actions is the dephosphorylation of myosin light chains, mediated by myosin light chain phosphatase (MLCP). This dephosphorylation leads to a reduction in myosin's ability to interact with actin, causing smooth muscle relaxation. As smooth muscle cells relax, blood vessels dilate, resulting in decreased vascular resistance and lowered blood pressure. This mechanism is particularly beneficial in managing hypertension, reducing the strain on the cardiovascular system.
By facilitating vasodilation and lowering blood pressure, Ginsentide TP1 promotes endothelial health. Chronic hypertension can lead to endothelial dysfunction, a precursor to atherosclerosis. The protective effects of Ginsentide TP1 against endothelial damage contribute to a lower risk of developing atherosclerotic plaques, thus enhancing overall cardiovascular health.
Moreover, the anti-inflammatory properties associated with NO production may further mitigate the progression of atherosclerosis. NO inhibits the expression of adhesion molecules on endothelial cells, which are critical for the recruitment of inflammatory cells to the vessel wall.
In addition to its vasodilatory effects, Ginsentide TP1 plays a crucial role in modulating platelet activity. By inhibiting the P2Y12 receptor on platelets, Ginsentide TP1 disrupts the signaling pathway that promotes platelet activation and aggregation. The P2Y12 receptor is a key player in the thrombotic process, primarily by facilitating the action of adenosine diphosphate (ADP).
When ADP binds to the P2Y12 receptor, it triggers a cascade of intracellular events that lead to platelet activation, shape change, and aggregation. By blocking this receptor, Ginsentide TP1 prevents ADP from exerting its effects, thereby reducing platelet activation. This inhibition diminishes the likelihood of thrombus formation, which is essential in preventing thromboembolic events.
Ginsentide TP1 demonstrates a multifaceted approach to promoting cardiovascular health through its activation of the PI3K-Akt pathway and subsequent effects on nitric oxide production, vascular relaxation, and platelet aggregation inhibition. By enhancing nitric oxide signalling, Ginsentide TP1 contributes to vasodilation, lowers blood pressure, and protects against endothelial damage, while its role in inhibiting platelet aggregation further reduces the risk of thromboembolic complications. These mechanisms underlying the therapeutic potential of Ginsentide TP1 in managing cardiovascular diseases and improving overall vascular function.
Lupin peptide P5 has emerged as a promising candidate in cholesterol management, exhibiting statin-like properties through its competitive inhibition of HMG-CoA reductase. By targeting this crucial enzyme in the mevalonate pathway, Lupin peptide P5 plays a significant role in reducing cholesterol production and enhancing the uptake of low-density lipoprotein (LDL) particles. This exploration delves deeper into its mechanisms of action and its interaction with PCSK9, along with the implications for cardiovascular health.
HMG-CoA reductase catalyses the conversion of HMG-CoA to mevalonate, a pivotal step in cholesterol biosynthesis. By inhibiting this enzyme, Lupin peptide P5 effectively decreases the synthesis of , leading to a cascade of metabolic changes. The reduction in mevalonate has several downstream effects. First, lower levels of mevalonate directly correlate with diminished cholesterol synthesis within the liver. This reduction not only lowers overall cholesterol levels but also impacts the production of very-low-density lipoprotein (VLDL), a precursor to LDL.
In addition, the decline in cholesterol levels triggers a compensatory mechanism in the liver, where the expression of LDL receptors (LDLr) is upregulated. This increase in LDLr on the cell surface enhances the liver’s capacity to clear LDL from circulation, resulting in reduced plasma LDL levels. Thus, the inhibition of HMG-CoA reductase by Lupin peptide P5 is a foundational mechanism in lowering cholesterol levels.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of LDL receptor levels. It functions by binding to the LDLr, which facilitates its degradation and reduces the receptor's availability for LDL uptake. When PCSK9 binds to the LDLr along with LDL particles, the complex is internalized into the cell. However, instead of separating the LDL from the LDLr, PCSK9 promotes the degradation of the entire complex in the lysosome. This results in fewer LDL receptors being recycled back to the cell surface, leading to a decrease in LDL uptake and an increase in cholesterol levels in the bloodstream.
Lupin peptide P5’s ability to counteract the detrimental effects of PCSK9 is a noteworthy aspect of its mechanism. By binding to PCSK9, Lupin peptide P5 prevents the formation of the PCSK9-LDLr complex, allowing for the normal endocytosis of LDL particles to be maintained. With PCSK9 inhibited, LDL receptors can effectively bind and internalise LDL particles from the bloodstream, restoring normal uptake processes. Furthermore, since PCSK9 is unable to facilitate the degradation of the LDLr, these receptors can be recycled back to the cell surface, thereby increasing the liver's capacity to clear LDL and further reducing plasma cholesterol levels.
The dual action of Lupin peptide P5—both inhibiting HMG-CoA reductase and blocking PCSK9—positions it as a potential adjunct to existing cholesterol-lowering therapies, such as statins and PCSK9 inhibitors. This combination could yield synergistic effects, optimising cholesterol management and enhancing cardiovascular protection.
Lupin peptide P5 represents a novel approach to cholesterol regulation, functioning through competitive inhibition of HMG-CoA reductase and counteracting PCSK9-mediated LDL receptor degradation. By lowering cholesterol production and enhancing LDL clearance, it offers a promising strategy for cardiovascular disease prevention.
We also have designed fusion proteins that have reporter genes for detection and diagnostic applications.
miRFP670nano is a fluorescent protein that is part of the miRFP (monomeric infrared fluorescent protein) family. These proteins are engineered to emit fluorescence in the near-infrared (NIR) range, specifically around 670 nm. miRFP670nano is designed for applications in live cell imaging and in vivo studies, allowing visualization and tracking of biological processes with minimal background interference and high tissue penetration due to the longer wavelength.
miRFP670nano is its monomeric structure. Unlike many traditional fluorescent proteins that tend to form dimers or oligomers, which can lead to aggregation and variability in fluorescent signal, miRFP670nano remains as a single, stable unit. This monomeric characteristic ensures a consistent and reliable fluorescence signal, which is critical for accurate imaging and analysis. The reduced likelihood of aggregation not only improves the quality of the imaging data but also facilitates the study of protein interactions within living cells. As a result, miRFP670nano is increasingly favored in various research applications, where clarity and precision are paramount.
GFP is widely used as a reporter gene to visualize and track proteins, cells, and organisms. GFP emits bright green fluorescence when exposed to ultraviolet or blue light. This fluorescence arises from the excitation of the chromophore, which then releases energy in the form of light as it returns to its ground state.