Linked Life Data

19810772

Source:http://linkedlifedata.com/resource/pubmed/id/19810772

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2009-11-3
pubmed:abstractText
Protein misfolding is a central mechanism for the development of neurodegenerative diseases and type 2 diabetes mellitus. The accumulation of misfolded alpha-synuclein protein inclusions in the Lewy bodies of Parkinson's disease is thought to play a key role in pathogenesis and disease progression. Similarly, the misfolding of the beta-cell hormone human islet amyloid polypeptide (h-IAPP) into toxic oligomers plays a central role in the induction of beta-cell apoptosis in the context of type 2 diabetes. In this study, we show that annexin A5 plays a role in interacting with and reducing the toxicity of the amyloidogenic proteins, h-IAPP and alpha-synuclein. We find that annexin A5 is coexpressed in human beta-cells and that exogenous annexin A5 reduces the level of h-IAPP-induced apoptosis in human islets by approximately 50% and in rodent beta-cells by approximately 90%. Experiments with transgenic expression of alpha-synuclein in Caenorhabditis elegans show that annexin A5 reduces alpha-synuclein inclusions in vivo. Using thioflavin T fluorescence, electron microscopy, and electron paramagnetic resonance, we provide evidence that substoichiometric amounts of annexin A5 inhibit h-IAPP and alpha-synuclein misfolding and fibril formation. We conclude that annexin A5 might act as a molecular safeguard against the formation of toxic amyloid aggregates.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10568-76
pubmed:dateRevised
2011-2-9
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Annexin A5 directly interacts with amyloidogenic proteins and reduces their toxicity.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural