1 research outputs found
Computational model of sphingolipids metabolism: a case study of Alzheimer's disease
Background: Sphingolipids - as suggested by the prefix in their name - are
mysterious molecules, which play surprisingly various roles in opposable
cellular processes, like autophagy, apoptosis, proliferation and
differentiation. Recently they have been also recognized as important
messengers in cellular signalling pathways. More importantly, sphingolipid
metabolism disorders were observed in various pathological conditions such as
cancer and neurodegeneration. Results: Existing formal models of sphingolipids
metabolism concentrates mostly on de novo ceramide synthesis or restrict their
focus to biochemical transformations of a particular subspecies. We propose
first comprehensive computational model of sphingolipid metabolism in human
tissue. In contrast to previous approaches we explicitly model
compartmentalization what allows emphasizing the differences among individual
organelles. Conclusions: Presented here model was validated by means of
recently proposed model analysis technics allowing for detection of most
sensitive and experimentally non-identifiable parameters and determination of
main sources of model variance. Moreover, we demonstrate the utility of the
model for the study of molecular processes underlying Alzheimer's disease