Dataset Information

CNSI

ABSTRACT: Metagenomic sequencing of cerebral spinal fluid (CSF)

PROVIDER: PRJEB81291 | ENA |

REPOSITORIES: ENA

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Dataset's files

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			Action	DRS
	ERR15142900_1.fastq.gz	Fastqsanger.gz
	ERR15142900_2.fastq.gz	Fastqsanger.gz
	ERR15143000_1.fastq.gz	Fastqsanger.gz
	ERR15143000_2.fastq.gz	Fastqsanger.gz
	ERR15142901_1.fastq.gz	Fastqsanger.gz

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Project description:Das2010 - Effect of a gamma-secretase inhibitor on Amyloid-beta dynamics This model is described in the article: Modeling effect of a ?-secretase inhibitor on amyloid-? dynamics reveals significant role of an amyloid clearance mechanism. Das R, Nachbar RB, Edelstein-Keshet L, Saltzman JS, Wiener MC, Bagchi A, Bailey J, Coombs D, Simon AJ, Hargreaves RJ, Cook JJ. Bull. Math. Biol. 2011 Jan; 73(1): 230-247 Abstract: Aggregation of the small peptide amyloid beta (A?) into oligomers and fibrils in the brain is believed to be a precursor to Alzheimer's disease. A? is produced via multiple proteolytic cleavages of amyloid precursor protein (APP), mediated by the enzymes ?- and ?-secretase. In this study, we examine the temporal dynamics of soluble (unaggregated) A? in the plasma and cerebral-spinal fluid (CSF) of rhesus monkeys treated with different oral doses of a ?-secretase inhibitor. A dose-dependent reduction of A? concentration was observed within hours of drug ingestion, for all doses tested. A? concentration in the CSF returned to its predrug level over the monitoring period. In contrast, A? concentration in the plasma exhibited an unexpected overshoot to as high as 200% of the predrug concentration, and this overshoot persisted as late as 72 hours post-drug ingestion. To account for these observations, we proposed and analyzed a minimal physiological model for A? dynamics that could fit the data. Our analysis suggests that the overshoot arises from the attenuation of an A? clearance mechanism, possibly due to the inhibitor. Our model predicts that the efficacy of A? clearance recovers to its basal (pretreatment) value with a characteristic time of >48 hours, matching the time-scale of the overshoot. These results point to the need for a more detailed investigation of soluble A? clearance mechanisms and their interaction with A?-reducing drugs. This model is hosted on BioModels Database and identified by: BIOMD0000000551. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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CNSI

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