總結(jié) |
The neurotrophins ("neuro" means nerve and "trophe" means nutrient) are afamily of soluble, basic growth factors which regulate neuronal development,maintenance, survival and death in the CNS and the PNS.1 NGF, the firstmember of the family to be discovered, was originally purified as a factor able to support survival of sympathetic and sensory spinal neurons in culture.2It is synthesized and secreted by sympathetic and sensory target organs andprovides trophic support to neurons as they reach their final target.3Neurotrophin secretion also increases in the nervous system following injury.Schwann cells, fibroblasts, and activated mast cells normally synthesize NGFconstitutively, however direct trauma and induced cytokines combine toincrease neurotrophin production in these cells after injury.4NGF is purified in three forms: the 7S, 2.5S and β. The 7S, 130 kDa, formoccurs naturally in mouse submaxillary glands, and is a multimeric protein composed of two α, oneβ and twoγ subunits. The name is derived from its sedimentation co-efficient, 7S. The biologically active subunitis the β, which is a 26 kDa dimer composed of two identical 120 amino acid chains held together by hydrophobic interactions.5 The 2.5S form is9 aminoacids shorter than the β form, because of proteolysis that occurs during thepurification process.6 The structural hallmark of all the neurotrophins is thecharacteristic arrangement of the disulfide bridges known as the cysteine knot,which has been found in other growth factors such as PDGF.7 There is a 95.8% homologybetween the rat and mouse forms, and a 85% homology between the human and mouse.NGF has been shown to regulate neuronal survival, development function and plasticity.8Recently, involvement of NGF in processes not involving neuronal cellshas been shown, such as asthma,9 psoriasis10 and wound healing.11 The biological effects of NGF are mediated by two receptors:TrkA, which is specific for NGF, and p75, which binds all the neurotrophins.12
|