Linked Life Data

12105112

Source:http://linkedlifedata.com/resource/pubmed/id/12105112

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-7-9
pubmed:abstractText
Alzheimer's disease (AD) is characterized by cerebrovascular deposition of the amyloid beta-peptide (A beta), which is derived from a larger beta-amyloid precursor protein (beta APP). Altered metabolism of beta APP, resulting in increased A beta production, appears central in the neuropathology of AD. The processing of the holoprotein beta APP by different "secretase" enzymes results in three major carboxyl-truncated species. One species, which results from the cleavage of beta APP by gamma-secretase, is secreted into the cerebrospinal fluid (CSF) and is called sAPP gamma as it contains an intact A beta domain. Moreover, AD is characterized by cholinergic dysfunction and the loss of synaptic proteins. Reports of an inverse relation between nicotine intake, due to cigarette smoking, and the incidence of AD prompted us to investigate the effects of nicotine on beta APP processing and synaptic proteins in rats and in cell culture. Nicotine, 1 and 8 mg/kg/day, doses commensurate with cigarette smoking, and a higher but well tolerated dose, respectively, was administered over 14 days to rats. Levels of sAPP in the CSF sample were evaluated by Western blot analysis. The higher dose significantly increased levels of total sAPP; however, both doses significantly reduced sAPP gamma, which contains the amyloidogenic portion of A beta. These actions were blocked by nicotinic receptor antagonism. Nicotinic antagonists alone had no effect on either total sAPP or sAPP gamma levels in CSF. Nicotine did not significantly change the intracellular levels of total beta APP in rat brain extracts, which is consistent with neuronal cell culture data. Similarly, levels of vesicular protein, such as synaptophysin, and presynaptic terminal protein SNAP-25 were unaffected by nicotine treatment both in vivo and in cell culture experiments. Taken together, these results suggest that nicotine modifies beta APP processing away from the formation of potentially amyloidogenic products, without altering the levels of synaptic proteins, and that this can potentially offer therapeutic potential for Alzheimer's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
965
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
364-72
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Nicotine reduces the secretion of Alzheimer's beta-amyloid precursor protein containing beta-amyloid peptide in the rat without altering synaptic proteins.
pubmed:affiliation
Laboratory of Molecular Neurogenetics, Department of Psychiatry and Neurology, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. dlahiri@iupui.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't