| pubmed-article:17309880 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0870134 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0599851 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0007589 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0285890 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0205369 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0392747 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0181586 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C0443172 | lld:lifeskim |
| pubmed-article:17309880 | lifeskim:mentions | umls-concept:C1511938 | lld:lifeskim |
| pubmed-article:17309880 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:17309880 | pubmed:dateCreated | 2007-4-6 | lld:pubmed |
| pubmed-article:17309880 | pubmed:abstractText | Missense mutations and extra copies of the alpha-Synuclein gene result in Parkinson disease (PD). Human stem and progenitor cells can be expanded from embryonic tissues and provide a source of non-transformed neural cells to explore the effects of these pathogenic mutations specifically in human nervous tissue. We over-expressed the wild type, A53T and A30P forms of alpha-synuclein in expanded populations of progenitors derived from the human fetal cortex. The protein localized in the nucleus and around microvesicles. Only the A53T form was acutely toxic, suggesting a unique vulnerability of these progenitors to this mutation. Interestingly, constitutive over-expression of wild-type alpha-synuclein progressively impaired the innate ability of progenitors to switch toward gliogenesis at later passages. To explore the effect of alpha-synuclein on neuronal subtypes selectively affected in PD, such as dopaminergic neurons, alpha-synuclein and its mutations were also over-expressed in terminally differentiating neuroectodermal cultures derived from human embryonic stem cells (hESC). Alpha-synuclein induced acute cytotoxicity and reduced the number of neurons expressing either tyrosine hydroxylase or gamma-aminobutyric acid over time. Consistent with the selective vulnerability of ventral midbrain dopaminergic neurons, alpha-synuclein cytotoxicity appeared most pronounced following FGF8/SHH specification and was decreased by inhibition of dopamine synthesis. Together, these data show that alpha-synuclein over-expressed in human neural embryonic cells results in patterns of degeneration that in some cases match features of Parkinson Disease. Thus, neural cells derived from hESC provide a useful model system to understand the development of alpha-synuclein-related pathologies and allow therapeutic drug screening. | lld:pubmed |
| pubmed-article:17309880 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17309880 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17309880 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:17309880 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17309880 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:17309880 | pubmed:issn | 0964-6906 | lld:pubmed |
| pubmed-article:17309880 | pubmed:author | pubmed-author:SvendsenClive... | lld:pubmed |
| pubmed-article:17309880 | pubmed:author | pubmed-author:ZhangSu-ChunS... | lld:pubmed |
| pubmed-article:17309880 | pubmed:author | pubmed-author:AebischerPatr... | lld:pubmed |
| pubmed-article:17309880 | pubmed:author | pubmed-author:SchneiderBern... | lld:pubmed |
| pubmed-article:17309880 | pubmed:author | pubmed-author:CapowskiEliza... | lld:pubmed |
| pubmed-article:17309880 | pubmed:author | pubmed-author:SeehusCorey... | lld:pubmed |
| pubmed-article:17309880 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17309880 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:17309880 | pubmed:volume | 16 | lld:pubmed |
| pubmed-article:17309880 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17309880 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17309880 | pubmed:pagination | 651-66 | lld:pubmed |
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| pubmed-article:17309880 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17309880 | pubmed:articleTitle | Over-expression of alpha-synuclein in human neural progenitors leads to specific changes in fate and differentiation. | lld:pubmed |
| pubmed-article:17309880 | pubmed:affiliation | Waisman Center and Department of Anatomy, University of Wisconsin, Madison, WI 53705, USA. | lld:pubmed |
| pubmed-article:17309880 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17309880 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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