Neurotrophic Factor.pptVIP

* 白血病抑制因子（LIF） oncostatin M 制瘤素 * It is implicated in the differentiation and survival of non-neuronal and neuronal cell types, including sensory, sympathetic, ciliary, and motor neurons.1,2 The non-neuronal effects include initiating an acute-phase response in liver cells, maintaining embryonic stem cells in an undifferentiated state, and producing a myotrophic effect on denervated skeletal muscles of mice. * * CNTF受体复合物中CNTFR?依靠GPI锚定在浆膜上，CNTF与CNTFR?结合，触发gp130、LIFR形成三元受体复合物。受体复合物中gp130和LIFR膜内区的保守序列触发JAK（Janus Kinases）和Tyk（(Protein-Tyrosine Kinase）的活化，随后诱导转录因子STAT（Signal Transducers and Activators of Transcription）家族的活化。 * * * * NTF是相对大的蛋白质，传输到CNS是一个显著的挑战。 BDNF有很好的耐药性；NGF高剂量产生耐药性。高剂量病人，产生严重毒性。 病人易产生CNTF抗体。 * * * * * * * * * * * * * * 磷脂酶C?（PLC?）起始的Ras-MAPK通路。PLC?结合在Trk的磷酸化酪氨酸785位（Y785）上。PLC?与TrkA结合导致酪氨酸磷酸化及PLC?活化，从而触发磷酸肌醇裂解产生两个信号分子：甘油二酯（diacul-glucerol, DAG）和三磷酸肌醇（inositoltrisphosphate, IP3），IP3与细胞内钙库的内质网模上的IP3受体（属于钙离子通道受体）结合，使Ca2+释放；DAG单独或与Ca2+一起激活蛋白激酶C（PKC），从而激活Ras-MAPK通路。 胰岛素受体底物（insulin receptor substrate, IRS）激活磷酸肌醇-3-激酶（PI3K）级联反应，进一步激活Ser/Thr蛋白激酶（AKT），产生生物效应。 * 在钝化的GDP-结合态和活化的GTP-结合态之间转变。 与GTP结合，使细胞生长保持活性，刺激细胞过量。 * * * * * * * * * * * * * The MAP kinase signaling pathway is mainly responsible for neurite growth, but also contributes to neuronal survival. The PI-3-kinase signaling pathway is crucial for neuronal survival, but also stimulates neurite growth. The PLC-γ signaling pathway regulates the intracellular level of Ca2+ ions by increasing the level of IP3 * * * * * To promote survival of cholinergic neurons: To promote survival of neurons As the same of NGF, BDNF also can promote survival of cholinergic neurons and differentiation of their phenotype in vitro. But both effect in different growth phases of cholingergic neurons, BDNF in forepart but NGF in anaphase. BDNF、NT-3 and NT-4 can promote survival of some motor cortical neurons and hippocampal neurons. Neurotrophins can promote survival of the neurons of NE-activated, DA-activated, 5-HT-