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Reduced sphingosine kinase-1 and enhanced sphingosine 1-phosphate lyase expression demonstrate deregulated sphingosine 1-phosphate signaling in Alzheimer's disease
- Source :
- Acta Neuropathologica Communications, Acta Neuropathologica Communications, BioMed Central part of Springer Science, 2014, 2 (1), pp.12. ⟨10.1186/2051-5960-2-12⟩, Acta Neuropathologica Communications, 2014, 2 (1), pp.12. ⟨10.1186/2051-5960-2-12⟩
- Publication Year :
- 2014
- Publisher :
- HAL CCSD, 2014.
-
Abstract
- International audience; BACKGROUND: The accumulation of beta amyloid (Aβ) peptides, a hallmark of Alzheimer's disease (AD) is related to mechanisms leading to neurodegeneration. Among its pleiotropic cellular effects, Aβ accumulation has been associated with a deregulation of sphingolipid metabolism. Sphingosine 1-phosphate (S1P) derived from sphingosine is emerging as a critical lipid mediator regulating various biological activities including cell proliferation, survival, migration, inflammation, or angiogenesis. S1P tissue level is low and kept under control through equilibrium between its synthesis mostly governed by sphingosine kinase-1 (SphK1) and its degradation by sphingosine 1-phosphate lyase (SPL). We have previously reported that Aβ peptides were able to decrease the activity of SphK1 in cell culture models, an effect that could be blocked by the prosurvival IGF-1/IGF-1R signaling. RESULTS: Herein, we report for the first time the expression of both SphK1 and SPL by immunohistochemistry in frontal and entorhinal cortices from 56 human AD brains. Immunohistochemical analysis revealed a decreased expression of SphK1 and an increased expression of SPL both correlated to amyloid deposits in the entorhinal cortex. Otherwise, analysis of brain tissue extracts showed a decrease of SphK1 expression in AD brains whereas SPL expression was increased. The content of IGF-1R, an activator of SphK1, was found decreased in AD brains as well as S1P1, the major receptor for S1P. CONCLUSIONS: Collectively, these results highlight the importance of S1P in AD suggesting the existence of a global deregulation of S1P signaling in this disease from its synthesis by SphK1 and degradation by SPL to its signaling by the S1P1 receptor.
- Subjects :
- Male
Statistics as Topic
chemistry.chemical_compound
0302 clinical medicine
Receptor
Neuropathology
Aged, 80 and over
Neurons
0303 health sciences
sphingoising1-phosphate lyase-neuropatholgy
Neurodegeneration
Brain
Sphingosine kinase-1
Middle Aged
Alzheimer's disease
Cell biology
Sphingosine 1-phosphate lyase
Phosphotransferases (Alcohol Group Acceptor)
Biochemistry
Sphingosine kinase 1
sphingosine kinase-1
Female
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Alzheimer’s disease
Alzheimer ' s disease
Signal Transduction
beta amyloid
Biology
Pathology and Forensic Medicine
03 medical and health sciences
Cellular and Molecular Neuroscience
Alzheimer Disease
medicine
Humans
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Sphingosine-1-phosphate
Aged
Aldehyde-Lyases
030304 developmental biology
Sphingolipids
Amyloid beta-Peptides
sphingolipids
Sphingosine
Cell growth
Research
Beta amyloid
Lipid signaling
medicine.disease
Sphingolipid
Gene Expression Regulation
chemistry
biology.protein
Neurology (clinical)
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20515960
- Database :
- OpenAIRE
- Journal :
- Acta Neuropathologica Communications, Acta Neuropathologica Communications, BioMed Central part of Springer Science, 2014, 2 (1), pp.12. ⟨10.1186/2051-5960-2-12⟩, Acta Neuropathologica Communications, 2014, 2 (1), pp.12. ⟨10.1186/2051-5960-2-12⟩
- Accession number :
- edsair.doi.dedup.....5cca08e783a923379d8756301661be9b