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Integrating Data for Modeling Biological Complexity

  • Sally Hunter
  • Carol Brayne

Abstract

This chapter describes how information relating to the interactions between molecules in complex biological pathways can be identified from the scientific literature and integrated into maps of functional relationships. The molecular biology of the amyloid precursor protein (APP) in the synaptic processes involved in normal cognitive function and neurodegenerative disease is used as a case study. The maps produced are interpreted with reference to basic concepts of biological regulation and control. Direct and indirect feedback relationships between the amyloid precursor protein, its proteolytic fragments and various processes that contribute to processes involved in synaptic modifications are identified. The contributions of the amyloid precursor protein and its proteolytic fragments are investigated with reference to disease pathways in Alzheimer disease and new perspectives on disease progression are highlighted. Mapping functional relationships in complex biological pathways is useful to summarize the current knowledge base, identify further targets for research, and for empirical experimental design and interpretation of results.

Keywords

Synaptic Plasticity Amyloid Precursor Protein Cholesterol Homeostasis Amyloid Precursor Protein Processing Proteolytic Fragment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ACh

muscarinic acetylcholine

AChE

acetylcholinesterase

AD

Alzheimerʼs disease

ADAM

a disintegrin and metalloproteinase

AICD

intracellular domain of APP

AMPA

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

APP

amyloid precursor protein

BACE

β-site APP cleaving enzyme

CTF

carboxy-terminal fragment

ECM

extracellular matrix

FAD

familial AD

LRP

lipoprotein receptor-related protein

LTD

long-term depression

LTP

long-term potentiation

MMP

matrix metalloproteinase

MeSH

medical subject heading

NMDA

N-methyl-d-aspartate

PS

presenilin

SAD

sporadic AD

nAChR

nicotinic acetylcholine receptor

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Copyright information

© Springer-Verlag 2014

Authors and Affiliations

  1. 1.Public Health and Primary CareUniversity of CambridgeCambridgeUK
  2. 2.Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK

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