Journal
NEUROSCIENCE
Volume 131, Issue 4, Pages 877-886Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2004.11.044
Keywords
neurodegeneration; cross-beta structure; plasmin
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Alzheimer's disease brain is characterized by the abundant presence of amyloid deposits. Accumulation of the major constituent of these deposits, amyloid-beta (A beta), has been associated with decreased neurotransmission, increased neuronal cell death, and with cognitive decline. The mechanisms underlying these phenomena have not yet been fully elucidated. We have previously shown that amyloid peptides like AV bind tissue-type plasminogen activator (tPA) and cause enhanced plasmin production. Here we describe the identification of five major neuronal cell-produced A beta-associated proteins and how A beta-stimulated plasmin formation affects their processing. These five proteins are all neuroendocrine factors (NEFs): chromogranins A, B and C; truncated chromogranin 13; and VGF. Plasminogen caused processing of A beta-bound (but not soluble) tPA, chromogranin B and VGF and the degradation products were released from AV. Processing of the neuroendocrine factors was dependent on tPA as it was largely abrogated in tPA(-/-) cells or in the presence of a specific tPA-inhibitor. If plasmin indeed produces NEF-derived peptides in vivo, some of these peptides may have biological activity, for instance in regulating neurotransmitter release that may affect the pathology of Alzheimer's disease. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.
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