CONTROL OF NERVE GROWTH FACTOR METABOLISM

神经生长因子代谢的控制

• 批准号: 3783161
• 负责人: JEREMY B TUTTLE
• 金额: --
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3783161
• 关键词: acetylcholine; angiotensin II; arginine vasopressin; biological signal transduction; calcium flux; cell growth regulation; chick embryo; cytokine; enzyme linked immunosorbent assay; gene expression; genetic transcription; growth factor receptors; immunocytochemistry; inhibitor /antagonist; interleukin 1; laboratory rat; messenger RNA; mixed tissue /cell culture; neurons; neurotrophic factors; northern blottings; phenylephrine; platelet derived growth factor; protein biosynthesis; protooncogene; receptor expression; secretion; smooth muscle; tissue /cell culture; vascular smooth muscle

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.

神经元依赖于被称为神经营养因子的蛋白质来维持正常 开发和维护。典型的例子是神经生长。 因子(NGF)，现在已知是至少三人组中的一员 相关的、非常有效且分布广泛的神经营养因子蛋白。而NGF则有 已被深入研究，但对NGF的合成知之甚少 向依赖神经元输送神经营养因子(S)的细胞。近期 平滑肌和神经胶质细胞调节NGF合成的演示允许 神经营养素的合成、分泌及其调控的研究。 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、多肽激动剂、神经递质)，内源性 事件(钙离子、原癌基因激活、细胞内信使)和 其他调节NGF合成的力量。NGF蛋白水平将是 用灵敏的双部位酶联免疫吸附试验测定。将对NGF mRNA进行检测 通过定性和半定量相结合的分析。NGF 将对分泌物及其要求进行检查，并且 NGF受体。 了解调控NGF传递的力量在 重要的是因为通过神经支配获得的因子的量 调节它们的生存、复杂性和连通性，即使是在成年。 目前还不清楚具体的紊乱或疾病反映了什么 神经营养因子的紊乱。然而，阿尔茨海默氏症，以及 也许与老年性痴呆有关，被认为涉及失落 基底前脑的神经生长因子依赖性神经元。NGF的不足是 被认为是导致或促成糖尿病神经病变的。膀胱 出口梗阻后的多动包括异常生长 神经生长因子对神经元的神经支配和反射功能的改变。 肥大的血管平滑肌异常超常神经支配 高血压也被认为是由增加的神经生长因子引起的 制作。神经营养素产生的细胞生物学知识 而分娩将为治疗或预防疟疾开辟新的途径 这些普遍而严重的临床问题。