Table 1.
Trophic factors and cytokines probed in alzheimer brain, ventricular fluid and cerebrospinal fluid samples.
| Trophic Factor | Abbreviation | Function |
|---|---|---|
| Basic Fibroblast Growth Factor | b–FGF | Present in basement membranes and sub-endothelial extracellular matrix. Regulates angiogenesis and cell survival, division, differentiation, and migration. Modulates nervous system development and wound healing. |
| Beta-Nerve Growth Factor | β–NGF | Neurotrophin family member that regulates survival and maintenance of sensory and sympathetic neurons. Implicated in neuronal growth, proliferation, differentiation and plasticity, as well as cognition. Functions through receptor tyrosine kinase. |
| Brain-Derived Neurotrophic Factor | BDNF | Neurotrophin family member that regulates synaptic transmission, activity-dependent plasticity and long-term potentiation in the hippocampus |
| Gastric Inhibitory Polypeptide | GIP-1 | Glucose-dependent insulinotropic peptide and secretin family member. Stimulates insulin secretion from pancreatic beta-cells following food ingestion. GIP receptors expressed in hippocampus, olfactory bulbs, and cerebellum. Promotes neural progenitor cell proliferation. |
| Ghrelin | GHRL | Stimulates hunger, craving, and growth hormone secretion from the pituitary. Functions in opposite ways compared to leptin. Essential for cognitive adaptations in changing environments. Receptor expressed in hypothalamus. |
| Glial Cell Line-Derived Neurotrophic Factor | GDNF | Isolated from glioma cells. Member of TGF-β superfamily. Neurotrophic factor that exerts neuroprotective and differentiation effects on dopaminergic and motor neurons |
| Glucagon-like Peptide 1 | GLP-1 | Incretin whose secretion is regulated by nutrients, e.g. carbohydrate, protein, and lipid. Promotes glucagon-dependent stimulation of insulin secretion, and survival and proliferation of pancreatic beta cells. Enhances insulin sensitivity and satiety. |
| Hepatocyte Growth Factor | HGF | Typically secreted by mesenchymal cells with actions on epithelial and endothelial cells. Mediates embryogenesis. Stimulates mitogenesis, cell motility, matrix invasion and angiogenesis via c-MET receptor tyrosine kinase. Regulates VEGF. Neuroprotective for cortical and hippocampal neurons during aging and ischemic injury. |
| Insulin | INS | Reduces blood glucose. Increases cellular permeability to monosaccharides, amino acids and fatty acids. Increases rates of glycolysis, pentose phosphate cycle, and glycogen synthesis in liver. |
| Leptin | LEP | Produced in adipocytes and regulates brain energy intake and expenditure, metabolism, and behavior. |
| Pancreatic Polypeptide (Human) | PP | Polypeptide secreted by PP endocrine cells in pancreas in response to hypoglycemia, fasting, or protein meal and decreased by glucose infusion or somatostatin. Closely related to neuropeptide Y and PP. |
| Peptide YY (tyrosine-tyrosine) | PYY | Secreted by intestinal L cells in response to feeding. Reduces appetite. Also produced in brainstem neurons, pancreatic islets. Improves nutrient absorption by slowing gastric motility and emptying. |
| Platelet-derived Growth Factor-AA | PDGF-AA | Regulates cell growth and angiogenesis, and mitogenic for glial and mesenchymal cells. Signals through PI3 Kinase to regulate cell growth and motility, tissue remodeling, differentiation, and migration. Maintains proliferation of oligodendrocyte progenitor cells. |
| Vascular Endothelial Growth Factor | VEGF | Stimulates angiogenesis and vasculogenesis and endothelial cell growth. Inhibits apoptosis and induces vascular permeability, revascularization of injured tissue, endothelial cell migration and proliferation. |
| Cytokine/Chemokine | Abbreviation | Function |
|---|---|---|
| Granulocyte Macrophage Colony-Stimulating Factor | GM-CSF | Stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. |
| Interferon-gamma | IFN-γ | Produced by innate NK cells, acquired antigen-specific cytotoxic CD4+ and effector CD8+ T cells. Activates macrophages and critical for innate and adaptive immune responses to intracellular pathogens, tumor control, and inhibition of viral replication. |
| Interferon-Gamma-Induced Protein | IP-10 | Produced by various cell types including monocytes, endothelial cells, fibroblasts, and keratinocytes. Induced by IFN-γ and TNF-α. Chemoattractant for activated T cells. |
| Interleukin-1, Beta | IL-1β | Produced by activated macrophages; mediates inflammatory responses, cell proliferation, and apoptosis. Induces Cox-2 in CNS, causing inflammatory pain |
| Interleukin-6 | IL-6 | Secreted by T cells and macrophages; triggers inflammation, acute phase response, fever. Anti-inflammatory effects include inhibiting TNF-α and IL-1, and activating IL-1Rα and IL-10. |
| Interleukin-8 | IL-8 | Made by macrophages and some epithelial and endothelial cells; Role in innate immune response. Major role in chemotaxis of neutrophils. Also mediates inflammatory response and angiogenesis. |
| Interleukin-10 | IL-10 | Produced by monocytes. Pleiotropic cytokine. As an anti-inflammatory cytokine, it inhibits macrophage and dendritic cell function, suppresses TNF-α. Acquires pro-inflammatory activity during immune response with IFN-α stimulation |
| Interleukin-16 | IL-16 | Secreted by lymphocytes. Pleiotropic cytokine. Functions as a chemo-attractant (CD4+ cells), modulates T cell activation, and inhibits HIV replication. |
| Interleukin-18 | IL-18 | Produced by macrophages and monocytes. Pro-inflammatory cytokine interacts with IL-12 to induce cell-mediated immune response with microbial infection and LPS, inducing severe inflammatory reactions. Stimulates NK and T cell release of IFN-γ, which activates macrophages. Inhibits IL4-dependent IgE, enhances B cell production. |
| Leukemia Inhibitory Factor | LIF | Induces myeloid cell differentiation, neuronal cell differentiation, and acute-phase protein synthesis. |
| Macrophage Inflammatory Protein 1 Beta | MIP-1β | Produced by macrophages. CCL4 chemokine that generates local inflammatory responses induces superoxide production by neutrophils. Chemotactic activity for lymphocytes, macrophages, NK cells, and monocytes with inflammation; down-regulates CCR5, inhibiting HIV-1 blocking. |
| Monocyte Chemotactic Protein-1 | MCP-1 | Expressed in monocytes, vascular endothelial cells, smooth muscle cells. CCL2 chemokine induces monocyte attraction, and degranulation of basophils with histamine release. Induced by IL-1, TNF-α, PDGF, TGF-β, and LIF |
| Stem Cell Factor | SCF | Regulates cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, and mast cell development, migration and function. Promotes phosphorylation of PIK3R1 and activation of AKT1. Aids in activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1 |
| Stromal Cell-Derived Factor-1α | SDF-1α | Expressed ubiquitously, except in blood cells. Small cytokine member of CXCL12 family of chemokines. Activates leukocytes due to strong chemotactic effects. Induced by pro-inflammatory stimuli, e.g. TNF-α and IL-1β. |
| TNF-Related Apoptosis Inducing Ligand | TRAIL | Secreted by macrophages, monocytes, neutrophils, T cells, NK cells after stimulation with LPS. CD4+ cells secrete TNF-α. Also made by astrocytes, microglial cells, smooth muscle cells, and fibroblasts. Mediates systemic inflammation, inhibits viral replication, and inhibits tumorigenesis. |
| Tumor Necrosis Factor-Alpha | TNF-α | Expressed broadly in tissues. Cytokine induces proapoptotic caspase activity by up-regulating pro-apoptotic Bcl proteins. Causes apoptosis in hepatocytes, neural cells, and thymocytes |