| http://purl.uniprot.org/citations/22331300 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22331300 | http://www.w3.org/2000/01/rdf-schema#comment | "Disruption of the blood-brain barrier (BBB) is a serious complication frequently encountered in neurodegenerative disorders. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. It remains unclear whether BBB is disrupted in INCL and if so, what might be the molecular mechanism(s) of this complication. We previously reported that the Ppt1-knockout (Ppt1-KO) mice that mimic INCL manifest high levels of oxidative stress and neuroinflammation. Recently, it has been reported that CD4(+) T-helper 17 (T(H)17) lymphocytes may mediate BBB disruption and neuroinflammation, although the precise molecular mechanism(s) remain unclear. We sought to determine: (i) whether the BBB is disrupted in Ppt1-KO mice, (ii) if so, do T(H)17-lymphocytes underlie this complication, and (iii) how might T(H)17 lymphocytes breach the BBB. Here, we report that the BBB is disrupted in Ppt1-KO mice and that T(H)17 lymphocytes producing IL-17A mediate disruption of the BBB by stimulating production of matrix metalloproteinases (MMPs), which degrade the tight junction proteins essential for maintaining BBB integrity. Importantly, dietary supplementation of resveratrol (RSV), a naturally occurring antioxidant/anti-inflammatory polyphenol, markedly reduced the levels of T(H)17 cells, IL-17A and MMPs, and elevated the levels of tight junction proteins, which improved the BBB integrity in Ppt1-KO mice. Intriguingly, we found that RSV suppressed the differentiation of CD4(+) T lymphocytes to IL-17A-positive T(H)17 cells. Our findings uncover a mechanism by which T(H)17 lymphocytes mediate BBB disruption and suggest that small molecules such as RSV that suppress T(H)17 differentiation are therapeutic targets for neurodegenerative disorders such as INCL."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/dds038"xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Chandra G."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Zhang Z."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Saha A."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Singh S.P."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Peng S."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Kong E."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Mukherjee A.B."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Munasinghe J."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/author | "Sarkar C."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/pages | "2233-2244"xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/title | "The blood-brain barrier is disrupted in a mouse model of infantile neuronal ceroid lipofuscinosis: amelioration by resveratrol."xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://purl.uniprot.org/core/volume | "21"xsd:string |
| http://purl.uniprot.org/citations/22331300 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22331300 |
| http://purl.uniprot.org/citations/22331300 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22331300 |
| http://purl.uniprot.org/uniprot/#_F7CTA8-mappedCitation-22331300 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22331300 |
| http://purl.uniprot.org/uniprot/#_B1B0P8-mappedCitation-22331300 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22331300 |
| http://purl.uniprot.org/uniprot/#_B1B0P9-mappedCitation-22331300 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22331300 |
| http://purl.uniprot.org/uniprot/#_O88531-mappedCitation-22331300 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22331300 |
| http://purl.uniprot.org/uniprot/#_Q3UFT5-mappedCitation-22331300 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22331300 |
| http://purl.uniprot.org/uniprot/#_Q3U6W3-mappedCitation-22331300 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22331300 |