Journal
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
Volume 2015, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2015/346783
Keywords
-
Categories
Funding
- Croatian Ministry of Science, Education and Sport [098-0000000-2448]
- Croatian Science Foundation [09/16]
- NIH [AG005138]
Ask authors/readers for more resources
Alzheimer's disease (AD), the most common chronic and progressive neurodegenerative disorder, is characterized by extracellular deposits of amyloid beta-peptides (A beta) and intracellular deposits of hyperphosphorylated tau (phospho-tau) protein. Ceramides, the major molecules of sphingolipid metabolism and lipid second messengers, have been associated with AD progression and pathology via A beta generation. Enhanced levels of ceramides directly increase A beta through stabilization of beta-secretase, the key enzyme in the amyloidogenic processing of A beta precursor protein (APP). As a positive feedback loop, the generated oligomeric and fibrillar A beta induces a further increase in ceramide levels by activating sphingomyelinases that catalyze the catabolic breakdown of sphingomyelin to ceramide. Evidence also supports important role of ceramides in neuronal apoptosis. Ceramides may initiate a cascade of biochemical alterations, which ultimately leads to neuronal death by diverse mechanisms, including depolarization and permeabilization of mitochondria, increased production of reactive oxygen species (ROS), cytochrome c release, Bcl-2 depletion, and caspase-3 activation, mainly by modulating intracellular signalling, particularly along the pathways related to Akt/PKB kinase and mitogen-activated protein kinases (MAPKs). This review summarizes recent findings related to the role of ceramides in oxidative stress-driven neuronal apoptosis and interplay with A beta in the cascade of events ending in neuronal degeneration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available