| http://purl.uniprot.org/citations/25339898 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25339898 | http://www.w3.org/2000/01/rdf-schema#comment | "Abnormal accumulation of filamentous α-synuclein (α-syn) in neurons, regarded as Lewy bodies (LBs), are a hallmark of Parkinson disease (PD). Although the exact mechanism(s) underlying LBs formation remains unknown, autophagy and ER stress response have emerged as two important pathways affecting α-syn aggregation. In present study we tested whether cells with the tetracycline-off inducible overexpression of α-syn and accumulating α-syn aggregates can benefit from autophagy activation elicited by nutrient deprivation (ND), since this approach was reported to effectively clear cellular polyglutamine aggregates. We found that nutrient deprivation of non-induced cells did not affect cell viability, but significantly activated autophagy reflected by increasing the level of autophagy marker LC3-II and autophagic flux and decrease of endogenous α-syn. Cells with induced α-syn expression alone displayed autophagy activation in an α-syn dose-dependent manner to reach a level comparable to that found in non-induced, nutrient deprived counterparts. Nutrient deprivation also activated autophagy further in α-syn induced cells, but the extent was decreased with increase of α-syn dose, indicating α-syn overexpression reduces the responsiveness of cells to nutrient deprivation. Moreover, the nutrient deprivation enhanced α-syn aggregations concomitant with significant increase of apoptosis as well as ER stress response, SREBP2 activation and cholesterolgenesis. Importantly, α-syn aggregate accumulation and other effects caused by nutrient deprivation were counteracted by knockdown of SREBP2, treatment with cholesterol lowering agent-lovastatin, or by GRP78 overexpression, which also caused decrease of SREBP2 activity. Similar results were obtained from studies of primary neurons with α-syn overexpression under nutrient deprivation. Together our findings suggested that down-regulation of SREBP2 activity might be a means to prevent α-syn aggregation in PD via reducing cholesterol levels."xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.org/dc/terms/identifier | "doi:10.3389/fnagi.2014.00268"xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/author | "Jiang P."xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/author | "Lin W.L."xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/author | "Gan M."xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/author | "Yen S.H."xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/name | "Front Aging Neurosci"xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/pages | "268"xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/title | "Nutrient deprivation induces alpha-synuclein aggregation through endoplasmic reticulum stress response and SREBP2 pathway."xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://purl.uniprot.org/core/volume | "6"xsd:string |
| http://purl.uniprot.org/citations/25339898 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25339898 |
| http://purl.uniprot.org/citations/25339898 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25339898 |
| http://purl.uniprot.org/uniprot/Q12772#attribution-5375E269133668B3D647C8912FCA6F17 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/25339898 |