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Journal of Neurology and Neurorehabilitation Research | Volume 3
August 23-24, 2018 | Paris, France
Neurology and Neurological Disorders
18
th
International Conference on
Neuronal SphK1 acetylates COX2 and contributes to pathogenesis in a model of Alzheimer’s Disease
Hee Kyung Jin
and
Jae-sung Bae
Kyungpook National University, South Korea
A
lthough many reports have revealed the importance of
defective microglia-mediated amyloid phagocytosis in
Alzheimer’s disease (AD), the underlying mechanism remains
to be explored. Here we demonstrate that neurons in the
brains of patients with AD and AD mice show reduction of
sphingosine kinase1 (SphK1), leading to defective microglial
phagocytosis and dysfunction of inflammation resolution due
to decreased secretion of specialized pro resolving mediators
(SPMs). Elevation of SphK1 increased SPMs secretion, especially
15-R-Lipoxin A4, by promoting acetylation of serine residue 565
(S565) of cyclooxygenase2 (COX2) using acetyl-CoA, resulting in
improvement of AD-like pathology in APP/PS1mice. In contrast,
conditional SphK1 deficiency in neurons reduced SPMs
secretion and abnormal phagocytosis similar to AD. Overall,
these results reveal a novel mechanism of SphK1 pathogenesis
in AD that leads to defective microglial phagocytosis due to
impaired SPMs secretion, and suggests that SphK1 in neurons
has acetyl-CoA dependent cytoplasmic acetyltransferase
activity towards COX2.
e:
hkjin@knu.ac.kr