Journal
NEUROBIOLOGY OF AGING
Volume 30, Issue 2, Pages 229-240Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2007.06.001
Keywords
Small heat shock proteins; Cerebral amyloid angiopathy; Alzheimer's disease; Hereditary cerebral hemorrhage with amyloidosis of the Dutch type; Inflammation
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Funding
- 'Internationale Stichting Alzheimer Onderzoek' (ISAO) [03517, 07510, 03509]
- Stichting Dioraphte
- Zon-MW Innovational Research [917.46.331]
- 'Hersenstichting Nederland' [11F03(2)11, 14F06.18]
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In hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), severe cerebral amyloid angiopathy (CAA) is associated With an inflammatory reaction. Small heat shock proteins (sHsps) are molecular chaperones and association of HspB8 with CAA in HCHWA-D has been observed. The aims of this study were to investigate (1) if other sHsps are associated with the pathological lesions in HCHWA-D brains. (2) if the amyloid-beta protein (A beta) increases production of sHsps in cultured cerebral cells and (3) if sHsps are involved in the cerebral inflammatory processes fit both Alzheimer's disease (AD) and HCHWA-D. We conclude that Hsp20, HspB8 and HspB2 are present in CAA in HCHWA-D. and that A beta did not affect cellular sHsps expression in cultured human brain pericytes and astrocytes. In addition, we demonstrated that Hsp20, HspB2 and HspB8 induced interleukin-6 production in cultured pericytes and astrocytes, which could be antagonized by dexamethasone, whereas other sHsps and A beta were inactive, suggesting that sHsps may be among the key mediators of the local inflammatory response associated with HCHWA-D and AD lesions. (C) 2007 Elsevier Inc. All ri-lits reserved.
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