PLASMALOPSYCHOSINE AS NEUROTROPHIC FACTOR

作为神经营养因子的缩醛磷脂

基本信息

批准号：
6629328
负责人：
Sen-itiroh Hakomori
金额：
$ 30.99万
依托单位：
PACIFIC NORTHWEST RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-02-04 至 2005-01-31
项目状态：
已结题

项目摘要

DESCRIPTION ( verbatim from the applicant's abstract): Fatty aldehyde conjugates have been limited previously to phospholipids in the form of plasmalogen. We recently found a novel plasmal conjugate linked to galactosyl-sphingosine (psychosine) or to cerebroside through cyclic acetal linkage; these were termed "plasmalopsychosine" (PLPS) and "plasmalocerebroside'' (PLCER), respectively. PLPS induces neurotrophic arid anti-apoptotic effects in PC 12 cells through TrkA activation and prolonged enhancement of mitogen-activated protein kinase. PLPS induces similar effects in neuroblastoma Neuro2a cells independent from the effect of Nerve Growth Factor (NGF). Thus, PLPS mimics NGF effect. We propose to study: (1) structural requirements for neurotrophic and anti-apoptotic effects of PLPS; (2) possible enzymatic conversion of PLCER to PLPS, and tissue distribution pattern of PLPS and PLCER; (3) comparison of neurotrophic effects of PLPS with effects of known neurotrophins in various neuronal cell lines; (4) interactions of PLPS with neurotrophin receptors and "glycosignaling domain" (GSD) which lead to activation of TrkA, p75NTR and other GSD-associated signal transducers; (5) anti-apoptotic activity of PLPS for normal, primary cultured neurons, (6) signal transduction pathways involved in the anti-apoptotic action of PLPS in cultured central and peripheral nervous system neurons, including kinase pathways (ERK, JNK, p38MAPK, AW PBK3, the pS3 tumor suppressor gene, members of the Bc1-2 family (Bc1-2, BC1-XL, Bax, Bad), caspases, [Ca2+]; free radical production and the mitochondrial function. Results of these studies may provide a basis for development of PLPS and its analogues as therapeutic reagents for neurodegenerative diseases and neuronal injury.

描述（逐字从申请人的摘要中）：脂肪醛以前以前限制了以磷脂的形式血浆原。我们最近发现了一种与半乳糖基 - 肾上腺素（Psychosine）或通过循环乙酰乙酸盐连锁;这些被称为“静脉假体”（PLP）和 “浆膜尿素”（PLCER）分别。PLPS诱导神经营养干旱通过TRKA激活，PC 12细胞中的抗凋亡效应并延长促分裂原激活蛋白激酶的增强。 PLP诱导类似的效果在神经母细胞瘤神经2a细胞中，独立于神经生长的作用因子（NGF）。因此，PLP模拟NGF效应。我们建议研究：（1）结构 PLP的神经营养和抗凋亡作用的要求；（2）可能 PLCer酶促转化为PLP和PLP的组织分布模式和plcer; （3）PLP的神经营养作用与已知的作用的比较各种神经元细胞系中的神经营养蛋白；（4）PLP与神经营养蛋白受体和“糖质信号结构域”（GSD）导致 TRKA，P75NTR和其他GSD相关信号传感器的激活；（5） PLP的抗凋亡活性对于正常的原发性培养神经元，（6） PLP的抗凋亡作用涉及的信号转导途径培养的中枢和周围神经系统神经元，包括激酶途径（ERK，JNK，P38MAPK，AW PBK3，PS3肿瘤抑制基因，成员 BC1-2家族（BC1-2，BC1-XL，BAX，BAX），caspase，[Ca2+];自由基生产和线粒体功能。这些研究的结果可能会提供开发PLP及其类似物作为治疗试剂的基础神经退行性疾病和神经元损伤。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Internal residue loss produced by rearrangement of a novel cationic glycosphingolipid, glyceroplasmalopsychosine, in collision-induced dissociation.

在碰撞诱导解离中，新型阳离子鞘糖脂甘油胞浆菌素重排产生的内部残基损失。

DOI：
10.1002/jms.485
发表时间：
2003
期刊：
Journal of mass spectrometry : JMS.
影响因子：
0
作者：
Tadano-Aritomi,Keiko;Hikita,Toshiyuki;Kubota,Masayuki;Kasama,Takeshi;Toma,Kazunori;Hakomori,Sen-Itiroh;Ishizuka,Ineo
通讯作者：
Ishizuka,Ineo

De-N-acetyllactotriaosylceramide as a novel cationic glycosphingolipid of bovine brain white matter: isolation and characterization.

脱-N-乙酰基乳三糖神经酰胺作为牛脑白质的新型阳离子鞘糖脂：分离和表征。

DOI：
10.1021/bi0504411
发表时间：
2005
期刊：
Biochemistry.
影响因子：
0
作者：
Hikita,Toshiyuki;Tadano-Aritomi,Keiko;Iida-Tanaka,Naoko;Ishizuka,Ineo;Hakomori,Senitiroh
通讯作者：
Hakomori,Senitiroh

A novel plasmal conjugate to glycerol and psychosine ("glyceroplasmalopsychosine"): isolation and characterization from bovine brain white matter.

一种新型血浆甘油和精神氨酸（“甘油胞浆精神氨酸”）结合物：从牛脑白质中分离和表征。