CONTROL OF NERVE GROWTH FACTOR METABOLISM

神经元依赖于蛋白质称为神经营养因子的正常 开发和维护。 典型的例子是神经生长 神经生长因子（NGF），现在已知是一组至少三个成员之一 相关的，非常有效和广泛的神经营养蛋白。 虽然NGF 虽然已经被深入研究，但对NGF的合成知之甚少。 向依赖性神经元传递神经营养因子的细胞。 最近 通过平滑肌和神经胶质细胞调节NGF合成的证明， 研究神经营养素合成、分泌及其调节。 培养的平滑肌将被用来揭示外在因素 （白细胞因子、细胞因子、肽激动剂、神经递质），内源性 事件（Ca2+、原癌基因激活、细胞内信使）和 调节NGF合成的其他力量。 神经生长因子蛋白的水平将是 用灵敏的双位点ELISA测定。 将检查NGF mRNA 通过定性和半定量分析相结合。 NGF 分泌和它的要求将被检查和任何作用的 NGF受体。 了解调节神经生长因子传递的力量的目标是， 重要的是，因为通过支配神经元获得的因子的量 调节着它们的生存、复杂性和连通性，即使在成年人中也是如此。 目前尚不清楚具体的失调或疾病反映了什么 神经营养因子紊乱。 然而，老年痴呆症， 可能与老年痴呆症有关，被假设涉及丧失 基底前脑的神经生长因子依赖神经元。 NGF缺乏症 被认为引起或促成糖尿病性神经病变。 膀胱 出口梗阻后的多动症涉及异常生长的 神经元支配和神经生长因子介导的反射功能的改变。 肥大血管平滑肌的异常神经支配 高血压也被假设来自于增加的神经生长因子 生产 神经营养素产生的细胞生物学知识 和交付将开辟新的途径，治疗或预防 这些普遍而严重的临床问题。

Neurons depend upon proteins known as neurotrophic factors for normal development and maintenance. The prototypial example is nerve growth factor (NGF), now known to be one member of a group of at least three related, very potent and widespread neurotrophin proteins. While NGF has been studied intensively, little is known about NGF synthesis by the cells that deliver neurotropic factor(s) to dependent neurons. Recent demonstration of regulated NGF synthesis by smooth muscle and glia allows study of neurotrophin synthesis, secretion and their regulation. Cultured smooth muscle will be used to reveal the extrinsic factors (leukokines, cytokines, peptide agonists, neurotransmitters), intrinsic events (Ca2+, protooncogene activation, intracellular messengers) and other forces regulating NGF synthesis. Levels of NGF protein will be measured with a sensitive two-site ELISA. NGF mRNA's will be examined via a combination of qualitative and semiquantitative analyses. NGF secretion and its requirements will be examined and any role of the receptor for NGF. The goal of understanding the forces that regulate NGF delivery in important because the amount of factor acquired by innervating neurons regulates their survival, complexity and connectivity, even in the adult. It is not yet clear what specific disorders or diseases reflect disturbances in neurotrophic factors. However, Alzheimer's disease, and perhaps related senile dementias, are hypothesized to involve loss of NGF-dependent neurons of the basal forebrain. NGF deficiencies are thought to cause or contribute to the diabetic neuropathies. Bladder hyperactivity following outlet obstruction involves anomalous growth of innervating neurons and alterations in reflex function mediated by NGF. An anomalous hyperinnervation of the hypertrophied vascular smooth muscle in hypertension is also hypothesized to derive from an increased NGF production. Knowledge of the cellular biology of neurotrophin production and delivery will open new avenues for the treatment or prevention of these prevalent and serious clinical problems.