At each step of the signaling cascade, various controlling factors are involved to regulate cellular actions, in order to respond effectively to cues about their changing internal and external environments.
The complex formed produces or releases second messengers that integrate and adapt the signal, amplifying it, by activating molecular targets, which in turn trigger effectors that will lead to the desired cellular response.
In the first one, first messenger cross through the cell membrane, binding and activating intracellular receptors localized at nucleus or cytosol, which then act as transcriptional factors regulating directly gene expression.
[1][4] Second messengers can be classified into three classes: The cellular response in signal transduction cascades involves alteration of the expression of effector genes or activation/inhibition of targeted proteins.
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.
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).
In general terms, platelet activation initiated by agonist takes to a signaling cascade that leads to an increase of the cytosolic calcium concentration.
This complex activates Iκκ kinase, which phosphorylates I-κB, and then allows the translocation of NF-κB to the nucleus and transcription of genes encoding cytokines, for example.
The canonical signaling involves binding of Wnt to Frizzled and LRP5 co-receptor, leading to GSK3 phosphorylation and inhibition of β-catenin degradation, resulting in its accumulation and translocation to the nucleus, where it acts as a transcription factor.
It is characterized by binding of Wnt to Frizzled and activation of G proteins and to an increase of intracellular levels of calcium through mechanisms involving PKC 50.
[70][71] During meiotic maturation, the LH peak that precedes ovulation activates MAPK pathway leading to gap junction disruption and breakdown of communication between the oocyte and the follicular cells.
This will lead to degradation of the follicular wall, but limiting the damage and ensuring that the rupture occurs in the appropriate location, releasing the oocyte into the fallopian tubes.
[78][79] The increased Ca2+ levels will induce the exocytosis of cortical granules that degrade ZP receptors, used by sperm to penetrate the oocyte, blocking polyspermy.
[81] Increasing our molecular knowledge of oocyte development mechanisms could improve the outcome of assisted reproduction procedures, facilitating conception.
FGF (Fibroblast Growth Factor) ligands bind to receptors tyrosine kinase, FGFR (Fibroblast Growth Factor Receptors), and form a stable complex with co-receptors HSPG (Heparan Sulphate Proteoglycans) that will promote autophosphorylation of the intracellular domain of FGFR and consequent activation of four main pathways: MAPK/ERK, PI3K, PLCγ and JAK/STAT.
BMP is also responsible for formation of extra-embryonic tissues before and during gastrulation, and for early mesoderm differentiation, when Activin and FGF pathways are activated.
The curation process of a biological pathway entails identifying and structuring content, mining information manually and/or computationally, and assembling a knowledgebase using appropriate software tools.
The increasing amount of genomic and molecular information is the basis for understanding higher-order biological systems, such as the cell and the organism, and their interactions with the environment, as well as for medical, industrial and other practical applications.
GenMAPP also offers innovative ways to display and share data by incorporating HTML export of analyses for entire sets of pathways as organized web pages.
[114] In short, GenMAPP provides a means to rapidly interrogate complex experimental data for pathway-level changes in a diverse range of organisms.
Tools have been developed to facilitate custom data entry and annotation by expert biologists, and to allow visualization and exploration of the finished dataset as an interactive process map.
The Reactome database containing a framework of possible reactions which, when combined with expression and enzyme kinetic data, provides the infrastructure for quantitative models, therefore, an integrated view of biological processes, which links such gene products and can be systematically mined by using bioinformatics applications.
With RNA interference, it is possible to distill the inferences contained in the experimental literature and primary databases into knowledge bases that consist of annotated representations of biological pathways.
These two databases also provide bioinformatics tools online to combine specific biochemical information on a certain organism and facilitate the interpretation of biological meanings for experimental data.
Parkinson's disease (PD) is multifactorial and clinically heterogeneous; the aetiology of the sporadic (and most common) form is still unclear and only a few molecular mechanisms have been clarified so far in the neurodegenerative cascade.
Cellular models that reproduce some of the features of the neurons that degenerate in PD have contributed to many advances in our comprehension of the pathogenic flow of the disease.
Classical cellular models appear to be the correct choice for preliminary studies on the molecular action of new drugs or potential toxins and for understanding the role of single genetic factors.
[132] Synaptic degeneration and death of nerve cells are defining features of Alzheimer's disease (AD), the most prevalent age-related neurodegenerative disorders.
In AD, neurons in the hippocampus and basal forebrain (brain regions that subserve learning and memory functions) are selectively vulnerable.
Studies of postmortem brain tissue from AD people have provided evidence for increased levels of oxidative stress, mitochondrial dysfunction and impaired glucose uptake in vulnerable neuronal populations.