Cell Trafficking
Independent Editorial
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Lymphocyte trafficking to the intestinal mucosa is governed by integrin-mediated adhesion between circulating lymphocytes and gut vascular endothelium. The alpha4beta7 integrin heterodimer, expressed on gut-homing lymphocyte subsets, binds selectively to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), expressed predominantly on intestinal lamina propria venules and Peyer’s patch high endothelial venules. This interaction, along with CCR9-CCL25 chemokine […]
Gut-selective Lymphocyte Trafficking
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Airway Pharmacology
Independent Editorial
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Bronchodilation in obstructive airway disease is achieved through two complementary receptor systems: beta-2 adrenergic receptors (beta-2-AR) and muscarinic acetylcholine receptors (mAChR), both modulating airway smooth muscle tone via opposing intracellular signalling cascades. Beta-2-AR is a Gs-coupled GPCR expressed on bronchial smooth muscle, mast cells, and epithelium; agonist binding activates adenylyl cyclase, elevating cAMP and activating […]
COPD/Asthma
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Kinase Pathway
Independent Editorial
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The MAPK signalling cascade (RAS-RAF-MEK-ERK) transmits extracellular growth signals from receptor tyrosine kinases to the nucleus, governing cell proliferation, differentiation, and survival. BRAF is a serine/threonine kinase in this cascade, normally activated transiently by RAS-GTP. The BRAF V600E substitution (valine to glutamic acid at codon 600) introduces a negative charge mimicking the phosphorylated activation loop, […]
Melanoma
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Intracellular Kinase
Independent Editorial
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Bruton’s tyrosine kinase (BTK) is a non-receptor cytoplasmic tyrosine kinase and critical component of the B-cell antigen receptor (BCR) signalling cascade. Following BCR engagement, BTK is recruited to the membrane and activated by upstream LYN and SYK kinases, subsequently phosphorylating phospholipase C-gamma-2 (PLCgamma2) to generate IP3 and DAG. This drives calcium mobilisation and PKC activation, […]
B-cell Malignancies
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Cell Surface Target
Independent Editorial
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CD20 is a non-glycosylated phosphoprotein expressed on the surface of pre-B cells, mature B lymphocytes, and most B-cell malignancies, but absent from haematopoietic stem cells and plasma cells. Its precise physiological function remains incompletely understood, though it likely functions as a calcium channel and is involved in B-cell activation and proliferation. The restricted expression pattern […]
B-cell disease
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Cell Cycle
Independent Editorial
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Cell cycle progression from G1 to S phase is governed by the cyclin D-CDK4/6 complex, which phosphorylates the retinoblastoma protein (Rb). Hyperphosphorylated Rb releases the transcription factor E2F, enabling transcription of S-phase entry genes and commitment to DNA replication and cell division. In hormone receptor-positive (HR+) breast cancer, oestrogen signalling drives cyclin D1 overexpression and […]
Breast Cancer
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Ion Channel
Independent Editorial
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Cystic fibrosis (CF) is caused by mutations in the CFTR gene encoding an ATP-binding cassette (ABC) transporter that functions as a cAMP-regulated chloride and bicarbonate channel on epithelial cell surfaces. Over 2,000 CFTR variants have been identified, classified into functional categories: class I (premature stop codons, no protein produced), class II (protein misfolding and premature […]
Cystic fibrosis
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Neuropeptide Pathway
Independent Editorial
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Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide predominantly expressed in trigeminal ganglion neurons, where it functions as a potent vasodilator and nociceptive modulator. During migraine attacks, activation of the trigeminovascular system — spanning trigeminal nerve fibres innervating the meningeal vasculature and their central projections — drives CGRP release into the cranial circulation and […]
Migraine
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Haemostasis
Independent Editorial
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The coagulation cascade proceeds via two convergent pathways — the extrinsic (tissue factor-initiated) and intrinsic (contact activation) pathways — both culminating in activation of factor Xa. Factor Xa, in complex with factor Va on phospholipid membranes (the prothrombinase complex), converts prothrombin (factor II) to thrombin (factor IIa) with markedly amplified efficiency. Thrombin then cleaves fibrinogen […]
DOACs
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Innate Immunity
Independent Editorial
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The complement system comprises over 30 proteins forming a proteolytic cascade of innate immunity, activated via three convergent pathways: the classical pathway (antibody-antigen complexes), the lectin pathway (pattern recognition by MBL/ficolins), and the alternative pathway (spontaneous C3 hydrolysis amplified on non-host surfaces). All three pathways converge on C3, generating C3b for opsonisation and C3a as […]
PNH
aHUS
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Neurotransmission
Independent Editorial
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Dopamine (DA) is a monoamine neurotransmitter with distinct functional roles across four major CNS projection systems: the mesolimbic pathway (nucleus accumbens — reward, motivation, positive symptoms of psychosis), mesocortical pathway (prefrontal cortex — executive function, working memory, negative symptoms), nigrostriatal pathway (basal ganglia — motor coordination, extrapyramidal function), and tuberoinfundibular pathway (hypothalamus-pituitary — prolactin regulation). […]
Psychiatry
Neurology
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Growth Factor Receptor
Independent Editorial
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The epidermal growth factor receptor (EGFR/ErbB1/HER1) is a transmembrane receptor tyrosine kinase activated by ligands including EGF, TGF-alpha, and amphiregulin. Ligand binding induces receptor homo- or heterodimerisation with other ErbB family members, kinase domain activation, and downstream signalling through RAS/MAPK (driving proliferation) and PI3K/AKT/mTOR (promoting survival and drug resistance). In NSCLC, activating mutations in the […]
Oncology
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Receptor Signalling
Independent Editorial
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Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from intestinal L-cells in response to nutrient ingestion, with a physiological half-life of under two minutes due to rapid degradation by dipeptidyl peptidase-4 (DPP-4). GLP-1 binds its cognate G-protein-coupled receptor (GLP-1R) on pancreatic beta-cells, activating adenylyl cyclase via Gs, elevating intracellular cAMP, and enhancing glucose-dependent insulin secretion. […]
Diabetes
Obesity
Cardiovascular risk
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Growth Factor Receptor
Independent Editorial
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Human epidermal growth factor receptor 2 (HER2/ErbB2) is a receptor tyrosine kinase that lacks an identified endogenous ligand and instead functions as the preferred dimerisation partner for all other ErbB family members (EGFR/HER1, HER3, HER4). HER2 gene amplification or protein overexpression, occurring in approximately 15-20% of breast cancers and 10-15% of gastric/gastro-oesophageal junction (GOJ) cancers, […]
Breast cancer
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Lipid Metabolism
Independent Editorial
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3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyses the rate-limiting step in the mevalonate pathway — the conversion of HMG-CoA to mevalonate — which is the committed step in hepatic cholesterol biosynthesis. Statins are structural analogues of HMG-CoA that competitively inhibit HMG-CoA reductase with approximately 1,000-fold greater affinity than the natural substrate. Reduced intracellular cholesterol synthesis in […]
Statins
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Cytokine Network
Independent Editorial
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Interleukin-4 (IL-4) and interleukin-13 (IL-13) are hallmark type 2 cytokines produced by Th2 lymphocytes, innate lymphoid cells type 2 (ILC2s), mast cells, basophils, and eosinophils. Epithelial barrier disruption and the resulting release of alarmins including TSLP, IL-33, and IL-25 initiates the type 2 inflammatory cascade by activating ILC2s and promoting Th2 differentiation. IL-4 signals through […]
Atopic dermatitis
Asthma
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Cytokine Network
Independent Editorial
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Interleukin-5 (IL-5) is the principal cytokine governing eosinophil biology — driving differentiation of eosinophil precursors in the bone marrow, promoting eosinophil priming and activation, and crucially extending eosinophil survival in peripheral blood and tissues through inhibition of apoptosis. IL-5 is produced primarily by Th2 lymphocytes, ILC2s, mast cells, and eosinophils themselves, creating an autocrine amplification […]
Severe Eosinophilic Asthma
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Cytokine Network
Independent Editorial
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Interleukin-6 (IL-6) is a pleiotropic cytokine with both pro-inflammatory and acute-phase regulatory roles, produced by macrophages, T-cells, fibroblasts, and endothelial cells. IL-6 signals through two mechanisms: classic signalling via membrane-bound IL-6 receptor alpha (mIL-6R, expressed on hepatocytes, leucocytes, and megakaryocytes) and trans-signalling via soluble IL-6R (sIL-6R), which enables IL-6 responsiveness in cells lacking mIL-6R expression. […]
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Intracellular Kinase
Independent Editorial
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The Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway is a central intracellular signalling cascade through which over 50 cytokines, growth factors, and interferons transmit their effects. Upon cytokine binding to its receptor, receptor-associated JAK kinases (JAK1, JAK2, JAK3, TYK2) undergo transphosphorylation, creating docking sites for STAT proteins. Activated STATs dimerize and translocate to […]
Rheumatoid Arthritis
Psoriatic Arthritis
Ulcerative Colitis
Atopic Dermatitis
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DNA Damage Response
Independent Editorial
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Poly(ADP-ribose) polymerase (PARP) enzymes, principally PARP1 and PARP2, are nuclear DNA damage sensors that recognise single-strand DNA breaks (SSBs) and catalyse poly-ADP-ribosylation of nearby proteins, recruiting the base excision repair (BER) machinery. PARP also plays roles in replication fork protection and regulation of transcription. In cells with intact homologous recombination (HR) — the high-fidelity repair […]
DNA Damage Response
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Protein Target
Independent Editorial
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PCSK9 (proprotein convertase subtilisin/kexin type 9) is a serine protease secreted primarily by hepatocytes that regulates LDL receptor (LDL-R) density on the hepatocyte surface. Following LDL-C uptake, the LDL-R normally recycles to the cell surface for repeated ligand binding. PCSK9 binds the LDL-R in the endosome, directing the receptor-PCSK9 complex to lysosomal degradation rather than […]
Lipid disorders
Cardiovascular risk
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Immune Checkpoint
Independent Editorial
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The programmed cell death protein-1 (PD-1) pathway is a critical adaptive immune checkpoint that maintains peripheral tolerance and prevents autoimmunity under physiological conditions. PD-1, expressed on activated T-cells, NK cells, and B-cells, interacts with its ligands PD-L1 (CD274, expressed broadly on tumour cells, stromal cells, and APCs) and PD-L2 (CD273, predominantly on APCs). PD-1 ligation […]
Oncology
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Hormone Cascade
Independent Editorial
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The renin-angiotensin-aldosterone system (RAAS) is a hormonal cascade governing blood pressure, fluid balance, and electrolyte homeostasis. Reduced renal perfusion pressure triggers juxtaglomerular cells to secrete renin, which cleaves hepatically-derived angiotensinogen to angiotensin I (Ang I). Angiotensin-converting enzyme (ACE), expressed predominantly in pulmonary vascular endothelium, converts Ang I to the bioactive angiotensin II (Ang II). Ang […]
Hypertension
Heart failure
CKD
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Bone Remodelling
Independent Editorial
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Bone remodelling is maintained by the tightly coupled activity of osteoblasts (bone formation) and osteoclasts (bone resorption), coordinated by the RANK/RANKL/OPG signalling axis. RANKL (receptor activator of NF-kappaB ligand), expressed on osteoblasts and bone marrow stromal cells, binds to RANK on osteoclast precursors and mature osteoclasts, driving osteoclastogenesis, osteoclast activation, and prolonged osteoclast survival. Osteoprotegerin […]
Osteoporosis
Bone metastases
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Immune Trafficking
Independent Editorial
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Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite generated by sphingosine kinase-mediated phosphorylation of sphingosine, which is in turn derived from ceramide catabolism. S1P is present at high concentrations in blood and lymph but at low levels in lymphoid organs, establishing a chemotactic gradient that drives lymphocyte egress. Naive and central memory T-cells and B-cells upregulate […]
MS/IBD
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Neurotransmission
Independent Editorial
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Serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (norepinephrine, NA) are monoamine neurotransmitters with central roles in mood regulation, cognition, autonomic function, and pain modulation. Following vesicular release into the synapse, both neurotransmitters are rapidly removed from the synaptic cleft by high-affinity, sodium-dependent reuptake transporters: SERT (serotonin transporter, encoded by SLC6A4) for 5-HT and NET (noradrenaline transporter, encoded […]
Depression
Pain
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Transporter
Independent Editorial
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Sodium-glucose cotransporter-2 (SGLT-2) is a high-capacity, low-affinity transporter expressed almost exclusively in the S1 segment of the proximal renal tubule, responsible for reabsorbing approximately 90% of the 180g of glucose filtered daily by the glomerulus. In type 2 diabetes, upregulated SGLT-2 expression contributes to sustained hyperglycaemia by increasing the renal glucose threshold. SGLT-2 inhibitors competitively […]
Diabetes
Heart failure
CKD
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Cytokine Network
Independent Editorial
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The IL-23/IL-17 axis is a central driver of immune-mediated inflammatory disease. IL-23, produced by dendritic cells and macrophages in response to microbial signals and tissue damage, acts as a master regulator — driving the differentiation and survival of Th17 cells. These Th17 cells produce IL-17A and IL-17F, which act on keratinocytes, synoviocytes, and osteoclasts to […]
Plaque Psoriasis
Psoriatic Arthritis
Ankylosing Spondylitis
Hidradenitis Suppurativa
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Cytokine Network
Independent Editorial
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Tumour necrosis factor-alpha (TNF-α) is a pleiotropic pro-inflammatory cytokine produced predominantly by activated macrophages, T-lymphocytes, and dendritic cells. Upon release, TNF-α binds to two distinct surface receptors — TNFR1 (ubiquitously expressed) and TNFR2 (primarily on immune and endothelial cells) — triggering downstream activation of NF-κB, MAPK, and caspase-dependent apoptotic pathways. This results in amplification of […]
Rheumatoid Arthritis
Ankylosing Spondylitis
Psoriatic Arthritis
Crohn's Disease
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Angiogenesis
Independent Editorial
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Vascular endothelial growth factor-A (VEGF-A) is the master regulator of pathological angiogenesis, secreted by tumour cells, stromal fibroblasts, and tumour-associated macrophages in response to hypoxia via hypoxia-inducible factor-1 alpha (HIF-1alpha). VEGF-A binds its primary signalling receptor VEGFR2 (KDR) on tumour vascular endothelium, activating downstream PI3K/AKT and RAS/MAPK pathways to drive endothelial cell proliferation, migration, tube […]
Oncology
Ophthalmology
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