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Aberrant sphingomyelin/ceramide metabolic-induced neuronal endosomal/lysosomal dysfunction: potential pathological consequences in age-related neurodegeneration.
- Source :
-
Advanced drug delivery reviews [Adv Drug Deliv Rev] 2003 Nov 14; Vol. 55 (11), pp. 1515-24. - Publication Year :
- 2003
-
Abstract
- Alterations in the trafficking and function of the endocytic pathway have been extensively documented to be one of the earliest pathological changes in sporadic Alzheimer's disease (AD). Although the pathophysiological consequences of these endosomal/lysosomal changes are currently unknown, several recent studies have suggested that such changes in endocytic function are able to cause a redistribution of several lysosomal hydrolases into early endosomes, leading to the overproduction of neurotoxic amyloid peptide. Recently, we and others have demonstrated that abnormal endocytic pathology within post-mitotic neurons can, in part, be attributed to alterations in sphingomyelin/ceramide metabolism, resulting in the intracellular accumulation of ceramide. Once inside the cell, the ability of ceramide to physically alter membrane structure, formation, and fusion, rather than serving solely as a lipid secondary messenger, may severely compromise normal endocytic trafficking. In this review, we will discuss the potential pathological effects of abnormal sphingomyelin/ceramide metabolism on intracellular vesicular transport in relation to both amyloid accumulation in AD and various neurodegenerative diseases associated with lysosomal abnormalities.
- Subjects :
- Aged
Alzheimer Disease metabolism
Alzheimer Disease pathology
Biological Transport
Cell Membrane metabolism
Endocytosis physiology
Humans
Neurodegenerative Diseases pathology
Ceramides metabolism
Endosomes metabolism
Lysosomes metabolism
Neurodegenerative Diseases metabolism
Sphingomyelins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0169-409X
- Volume :
- 55
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Advanced drug delivery reviews
- Publication Type :
- Academic Journal
- Accession number :
- 14597144
- Full Text :
- https://doi.org/10.1016/j.addr.2003.07.007