NEUROMUSCULAR AND CENTRAL NERVOUS SYSTEM DISEASES AND THEIR EXPERIMENTAL MODELS

神经肌肉和中枢神经系统疾病及其实验模型

• 批准号: 3881732
• 负责人: M C DALAKAS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 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/3881732
• 关键词: AIDS dementia complex; Pongidae; Retroviridae; Retroviridae disease; aging; albumins; amyloid proteins; antiviral antibody; astrocytes; biomarker; biopsy; cats; cell adhesion molecules; central nervous system disorders; glycolipids; human subject; immunocytochemistry; immunoglobulin M; immunopathology diagnosis; inflammation; laminin; lymphatic tissue; lymphocyte; macrophage; mitochondria; monoclonal antibody; muscle cells; myelin; myelinopathy; myoblasts; myofibrils; natural killer cells; nervous system disorder; nervous system disorder diagnosis; neuromuscular disorder; peripheral nervous system disorders; point mutation; polymerase chain reaction; regeneration; simian AIDSs; simian immunodeficiency virus; simian virus; thymosin; tissue /cell culture

Immunocytochemical studies were conducted using specific antibodies to thymic peptides to investigate the interaction of the immune system with the central and peripheral nervous systems. Thymosin beta 4, an immunomodulating thymic polypeptide, was found to be a common antigen shared by macrophages, dendritic lymphoid cells and the myelin producing cells in the CNS (oligodendrocytes) and the PNS (Schwann cells). Prothymosin, a nuclear protein, and thymosin-a1, were found present in astrocytes of normal human brain and could play a role in cell proliferation and gliosis. The IgM of certain patients with paraproteinemic polyneuropathies has been identified as a specific antibody to acid intraneural injection of IgM in the sciatic nerve of the cat induced demyelination suggesting a direct role in the pathogenesis of the neuropathy. The nature of amyloid protein in patients with "sporadic" amyloid polyneuropathy was identified using specific antibodies to amyloid proteins; point mutations and direct sequencing of prealbumin genes, the precursor protein, were studied in the amyloid tissue using the polymerase chain reaction. The mechanism of inflammatory myopathy in monkeys with immunodeficiency (Simian AIDS) cause by SRV-1 and SIV-1 retroviruses, was studied. Antibodies to SRV-1 immunoreacted with inflammatory cells invading muscle fibers; SRV-1 was capable of infecting myoblasts in tissue culture without exerting a cytopathic effect in the muscle. The role of SIV-1 is similarly studied. The effect of aging on the neuromuscular system of monkeys from age 5 to 25 is being studied with a detailed morphological and morphometrical analysis of their muscle and nerve biopsies. The mechanism of muscle regeneration is studied examining markers on satellite cells including the role of adhesion on molecules such as laminin, N-CAM, and ICAM. The monoclonal antibody Leu-19 (NKH) that identifies natural killer cells was found to share common antigenic determinants with the satellite muscle cells. NKH also stains regenerating muscle fibers and could play a role in muscle regeneration. The induction of abnormal mitochondria in the muscle by several nucleoside analogues is investigated in the muscle fibers in tissue culture.

使用特异性抗体进行免疫细胞化学研究 胸腺肽来研究免疫系统与 中枢和周围神经系统。胸腺素β4， 免疫调节胸腺多肽，被发现是一种常见抗原 由巨噬细胞、树突状淋巴细胞和产生髓磷脂的细胞共享 CNS（少突胶质细胞）和 PNS（雪旺细胞）中的细胞。 胸腺肽原（一种核蛋白）和胸腺肽-a1 被发现存在于 正常人脑的星形胶质细胞，可以在细胞中发挥作用 增殖和神经胶质增生。某些异常蛋白血症患者的 IgM 多发性神经病已被确定为针对酸的特异性抗体 猫坐骨神经神经内注射 IgM 诱导 脱髓鞘提示在该疾病的发病机制中具有直接作用 神经病。 “散发”患者淀粉样蛋白的本质 使用淀粉样蛋白特异性抗体鉴定淀粉样多发性神经病 蛋白质；前白蛋白基因的点突变和直接测序 使用聚合酶在淀粉样蛋白组织中研究前体蛋白 连锁反应。猴炎症性肌病的机制 由 SRV-1 和 SIV-1 逆转录病毒引起的免疫缺陷（猿猴艾滋病） 研究过。 SRV-1 抗体与入侵的炎症细胞发生免疫反应 肌肉纤维； SRV-1能够感染组织培养中的成肌细胞 而不在肌肉中发挥细胞病变作用。 SIV-1的作用是 类似地研究过。衰老对神经肌肉系统的影响 正在对 5 至 25 岁的猴子进行详细的形态学和 对他们的肌肉和神经活检进行形态测量分析。机制 通过检查卫星细胞上的标记来研究肌肉再生的过程 包括层粘连蛋白、N-CAM 等分子的粘附作用 ICAM。识别自然杀伤细胞的单克隆抗体 Leu-19 (NKH) 发现细胞与卫星具有共同的抗原决定簇 肌肉细胞。 NKH 还可对再生肌肉纤维进行染色，并可发挥作用 在肌肉再生中的作用。诱导线粒体异常 在肌肉纤维中研究了几种核苷类似物对肌肉的影响 在组织培养中。