http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
허혈성 신경세포손상이 아밀로이드 전구단백질의 대사에 미치는 영향
이필휴,황은미,묵인희,허균,최일생 대한신경과학회 2005 대한신경과학회지 Vol.23 No.2
Background: In spite of the different pathogenesis and exclusive respect in the diagnosis of Alzheimer's disease (AD) and vascular dementia (VaD), recent epidemiological and pathological studies indicates that ischemic stroke have an important role in the pathogenesis of both VaD and AD. However,the association of ischemic stroke and AD on the cellular and molecular level is still unknown. We evaluated the effect of ischemic neuronal insult on the regulation of amyloid precursor protein (APP) processing. Methods: We used an in vitro model of cerebral ischemia (oxygen-glucose deprivation, OGD) to evaluate the effect of ischemic insult on the amyloidogenic and non-amyloidogenic pathways using human neuroblastoma cell line, SH-SY5Y, and primary cultured cells of Tg2576 APP transgenic mouse. Results: Ischemic insult significantly increased the beta amyloid (Aβ) production in the primary cultured cells of Tg2576 APP transgenic mice (p<0.001). A disintegrin and metalloprotease 10 (ADAM 10), a candidate of α- secretase, was markedly increased in the early stage of ischemic insult (up to 2 hours of OGD, p<0.001; 4 hours of OGD, p<0.05), which was followed by the decreased level of ADAM 10 expression in a later stage (p<0.001). However, the protein and mRNA expression of β-site cleavage enzyme (BACE) and BACE activity were not significantly different between the group of ischemic insult and control. By contrast, the activity of γ-secretase was significantly increased after 4 hours of ischemic insult, as compared to controls. Conclusions: This study demonstrates that the ischemic neuronal insults increase the production of Aβ via activation of the amyloidogenic pathway, which may link the role of ischemic insults to the pathogenesis of AD.
이필휴,박현정 대한신경과학회 2009 Journal of Clinical Neurology Vol.5 No.1
Parkinson’s disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases representative of α-synucleinopathies characterized pathologically by α-synuclein-abundant Lewy bodies and glial cytoplasmic inclusions, respectively. Embryonic stem cells, fetal mesencephalic neurons, and neural stem cells have been introduced as restorative strategies in PD animals and patients, but ethical and immunological problems as well as the serious side effects of tumorigenesis and disabling dyskinesia have limited clinical application of these stem cells. Meanwhile, cell therapy using mesenchymal stem cells (MSCs) is attractive clinically because these cells are free from ethical and immunological problems. MSCs are present in adult bone marrow and represent <0.01% of all nucleated bone marrow cells. MSCs are themselves capable of multipotency, differentiating under appropriate conditions into chondrocytes, skeletal myocytes, and neurons. According to recent studies, the neuroprotective effect of MSCs is mediated by their ability to produce various trophic factors that contribute to functional recovery, neuronal cell survival, and stimulation of endogenous regeneration and by immunoregulatory properties that not only inhibit nearly all cells participating in the immune response cell-cell-contact-dependent mechanism, but also release various soluble factors associated with immunosuppressive activity. However, the use of MSCs as neuroprotectives in PD and MSA has seldom been studied. Here we comprehensively review recent advances in the therapeutic roles of MSCs in PD and MSA, especially focusing on their neuroprotective properties and use in disease-modifying therapeutic strategies.