Dataset Information

Human CSF peptidomics of gamma secretase inhibition

ABSTRACT: Fifteen human healthy volunteers, divided into three groups, received a single dose of placebo or either 140 mg or 280 mg of the ?-secretase inhibitor semagacestat (LY450139). Endogenous peptides in CSF, sampled prior to administration of the drug and at six subsequent time points, were analyzed by liquid chromatography coupled to mass spectrometry, using isobaric labeling based on the tandem mass tag approach for relative quantification.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Johan Gobom

PROVIDER: MSV000080870 | MassIVE | Sat Apr 01 03:21:00 BST 2017

SECONDARY ACCESSION(S): PXD003075

REPOSITORIES: MassIVE

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Publications

A single dose of the γ-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans.

Hölttä Mikko M Dean Robert A RA Siemers Eric E Mawuenyega Kwasi G KG Sigurdson Wendy W May Patrick C PC Holtzman David M DM Portelius Erik E Zetterberg Henrik H Bateman Randall J RJ Blennow Kaj K Gobom Johan J

Alzheimer's research & therapy 20160307 1

<h4>Background</h4>In Alzheimer's disease, beta-amyloid peptides in the brain aggregate into toxic oligomers and plaques, a process which is associated with neuronal degeneration, memory loss, and cognitive decline. One therapeutic strategy is to decrease the production of potentially toxic beta-amyloid species by the use of inhibitors or modulators of the enzymes that produce beta-amyloid from amyloid precursor protein (APP). The failures of several such drug candidates by lack of effect or und ...[more]

PMID: 26948580

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