期刊
NEUROTOXICITY RESEARCH
卷 10, 期 1, 页码 1-10出版社
SPRINGER
DOI: 10.1007/BF03033329
关键词
Parkinson's disease; Alzheimer's disease; Lewy bodies; alpha-synuclein; p-tau; MPTP
资金
- NINDS NIH HHS [NS-45326, NS-41555, NS-34914] Funding Source: Medline
Alzheimer's disease (AD) is characterized, in part, by intracellular neurofibrillary tangles composed of hyperphosphorylated filamentous aggregates of the microtubule-associated protein, Tau. Such hyperphosphorylated Tau is also found in Lewy bodies (LBs), and cytoplasmic inclusion bodies in certain forms of Parkinson's disease (PD). Further, LBs also contain aggregates of alpha-synuclein (alpha-Syn), also a microtubule-associated protein, which has been linked to the genesis of PD. To investigate a specific correlation between Tau phosphorylation and alpha-Syn, we generated a SH-SY5Y cell line that stably expresses human wild type alpha-Syn. Protein expression levels in the stably transfected cell line (SH alpha-Syn) were within the physiological range of a-Syn expression found in Substantia nigra. We show here, in the MPP+ (1-methyl-4-phenylpyridinium ion) cell model of parkinsonism, a time- and dose-dependent increase in the hyperphosphorylation of Tau at pSer396/404 (PHF-1-reactive Tau, p-Tau), concomitant with increased accumulation of alpha-Syn, upon treatment of cells with the neurotoxin. This increase in p-Tau was strictly dependent on the presence of alpha-Syn, since in transfected cells not expressing any alpha-Syn, MPP+ failed to induce an increase in PBF-1-reactive Tau. The production of p-Tau caused increased cytotoxicity as indexed by reduced cell viability. Moreover, in the absence of alpha-Syn, the cells were more resistant to MPP+-induced cell death. The increased levels of both p-Tau and alpha-Syn led to diminished levels of these proteins associated with the cytoskeleton, which was accompanied by enhanced presence of the proteins in the cytoskeletal-free fractions. These data indicate that alpha-Syn and p-Tau modulate the pathogenicity of one another, suggesting a novel convergent mechanism of neurodegeneration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据