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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Biochemical cascade | 3/9 | https://en.wikipedia.org/wiki/Biochemical_cascade | reference | science, encyclopedia | 2026-05-05T10:46:07.942614+00:00 | kb-cron |
=== Neurons === Purinergic signalling has an essential role at interactions between neurons and glia cells, allowing these to detect action potentials and modulate neuronal activity, contributing for intra and extracellular homeostasis regulation. Besides purinergic neurotransmitter, ATP acts as a trophic factor at cellular development and growth, being involved on microglia activation and migration, and also on axonal myelination by oligodendrocytes. There are two main types of purinergic receptors, P1 binding to adenosine, and P2 binding to ATP or ADP, presenting different signalling cascades. The Nrf2/ARE signalling pathway has a fundamental role at fighting against oxidative stress, to which neurons are especially vulnerable due to its high oxygen consumption and high lipid content. This neuroprotective pathway involves control of neuronal activity by perisynaptic astrocytes and neuronal glutamate release, with the establishment of tripartite synapses. The Nrf2/ARE activation leads to a higher expression of enzymes involved in glutathione syntheses and metabolism, that have a key role in antioxidant response. The LKB1/NUAK1 signalling pathway regulates terminal axon branching at cortical neurons, via local immobilized mitochondria capture. Besides NUAK1, LKB1 kinase acts under other effectors enzymes as SAD-A/B and MARK, therefore regulating neuronal polarization and axonal growth, respectively. These kinase cascades implicates also Tau and others MAP. An extended knowledge of these and others neuronal pathways could provide new potential therapeutic targets for several neurodegenerative chronic diseases as Alzheimer's, Parkinson's and Huntington's disease, and also amyotrophic lateral sclerosis.
=== Blood cells === The blood cells (erythrocytes, leukocytes and platelets) are produced by hematopoiesis. The erythrocytes have as main function the O2 delivery to the tissues, and this transfer occurs by diffusion and is determined by the O2 tension (PO2). The erythrocyte is able to feel the tissue need for O2 and cause a change in vascular caliber, through the pathway of ATP release, which requires an increase in cAMP, and are regulated by the phosphodiesterase (PDE). This pathway can be triggered via two mechanisms: physiological stimulus (like reduced O2 tension) and activation of the prostacyclin receptor (IPR). This pathway includes heterotrimeric G proteins, adenylyl cyclase (AC), protein kinase A (PKA), cystic fibrosis transmembrane conductance regulator (CFTR), and a final conduit that transport ATP to vascular lumen (pannexin 1 or voltage-dependent anion channel (VDAC)). The released ATP acts on purinergic receptors on endothelial cells, triggering the synthesis and release of several vasodilators, like nitric oxide (NO) and prostacyclin (PGI2). The current model of leukocyte adhesion cascade includes many steps mentioned in Table 1. The integrin-mediated adhesion of leukocytes to endothelial cells is related with morphological changes in both leukocytes and endothelial cells, which together support leukocyte migration through the venular walls. Rho and Ras small GTPases are involved in the principal leukocyte signaling pathways underlying chemokine-stimulated integrin-dependent adhesion, and have important roles in regulating cell shape, adhesion and motility.
After a vascular injury occurs, platelets are activated by locally exposed collagen (glycoprotein (GP) VI receptor), locally generated thrombin (PAR1 and PAR4 receptors), platelet-derived thromboxane A2 (TxA2) (TP receptor) and ADP (P2Y1 and P2Y12 receptors) that is either released from damaged cells or secreted from platelet dense granules. The von Willebrand factor (VWF) serves as an essential accessory molecule. In general terms, platelet activation initiated by agonist takes to a signaling cascade that leads to an increase of the cytosolic calcium concentration. Consequently, the integrin αIIbβ3 is activated and the binding to fibrinogen allows the aggregation of platelets to each other. The increase of cytosolic calcium also leads to shape change and TxA2 synthesis, leading to signal amplification.