Title:Ceramide and Sphingosine-1-Phosphate in Cell Death Pathways : Relevance to the Pathogenesis of Alzheimer's Disease
Volume: 13
Issue: 11
Author(s): Sankha Shubhra Chakrabarti, Aritri Bir, Jit Poddar, Maitrayee Sinha, Anirban Ganguly and Sasanka Chakrabarti
Affiliation:
Keywords:
Sphingomyelin, Ceramide, Sphingosine-1-phosphate, Mitochondria, Amyloid beta protein, Apoptosis, Necroptosis,
Alzheimer's disease.
Abstract: The metabolic turnover of sphingolipids produces several signaling molecules that profoundly
affect the proliferation, differentiation and death of cells. In particular, an enormous body of
information is available that defines the varied role of ceramide and sphingosine-1-phosphate in cell
death and survival. This review specifically examines the role of ceramide and sphingosine-1-
phosphate in triggering neuronal death in Alzheimer's disease by analyzing the data from post-mortem
studies and experimental research. There is compelling evidence that ceramide plays a key role in the
neurodegeneration and amyloidogenesis occurring in the brain in Alzheimer's disease. Further, it appears
that ceramide and amyloid beta protein orchestrate an attack on mitochondria to set in the pathways
of cell death. However, the complexity of metabolic and signaling pathways of sphingolipid derivatives
precludes an immediate identification of effective drug targets for the therapy of Alzheimer's
disease.
