The public health burden of
metabolic syndrome (MetS), a multiplex risk factor that arises from
insulin resistance accompanying abnormal adipose conditions, and
Alzheimer's disease (AD), the most common form of
dementia, continues to expand. Current available
therapies for these disorders are of limited effectiveness. Recent findings have indicated that alternations in
sphingolipid metabolism contribute to the development of these pathologies.
Sphingolipids are major constituents of the plasma membrane, where they are known to form several types of microdomains, and are potent regulators for a variety of physiological processes. Many groups, including ours, have demonstrated that membrane
sphingolipids, especially
ceramide and its metabolites such as
ceramide 1-phosphate, have roles in
arteriosclerosis,
obesity, diabetes, and
inflammation associated with MetS. Aberrant
sphingolipid profiles have been observed in human AD brains, and accumulated evidence has demonstrated that changes in membrane properties induced by defective
sphingolipid metabolism impair generation and degradation of
amyloid-β
peptide (Aβ), a pathogenic agent of AD. In this review, we summarize current knowledge and pathophysiological implications of the roles of SLs in MetS and AD, to provide insight into the SL metabolic pathways as potential targets for
therapy of these diseases. This article is part of a Special Issue entitled New Frontiers in
Sphingolipid Biology.